Affinage

PPARGC1A

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha · UniProt Q9UBK2

Round 2 corrected
Length
798 aa
Mass
91.0 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPARGC1A (PGC-1α) is a transcriptional coactivator that orchestrates adaptive energy metabolism by docking onto nuclear receptors and transcription factors—including PPARγ, PPARα, PPARβ/δ, NRF-1, ERRα, HNF4α, IRF4, and MEF2—and recruiting the histone acetyltransferases SRC-1 and CBP/p300 to activate target gene programs governing mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation, thermogenesis (UCP1/UCP3), hepatic gluconeogenesis (PEPCK/G6Pase), fiber-type switching, kynurenine metabolism, ureagenesis, peroxisomal biogenesis, autophagy/mitophagy, ribosomal RNA transcription, and angiogenesis (PMID:9529258, PMID:10412986, PMID:10558993, PMID:21059926, PMID:31441382, PMID:28819135). Its activity is tuned by post-translational modifications: p38 MAPK phosphorylation stabilizes and activates the protein, SIRT1-mediated NAD⁺-dependent deacetylation selectively potentiates gluconeogenic outputs, SUMOylation at K183 attenuates transactivation by promoting corepressor RIP140 interaction, and DNMT3B-catalyzed non-CpG promoter methylation silences PPARGC1A transcription (PMID:11741533, PMID:15744310, PMID:19625249, PMID:19723495). Alternative promoter usage and splicing generate functionally distinct isoforms—PGC-1α1 drives oxidative and kynurenine-metabolizing programs while PGC-1α4 induces IGF1, represses myostatin to promote muscle hypertrophy, and confers anti-apoptotic hepatic functions—and muscle-derived PGC-1α stimulates secretion of the myokine irisin (FNDC5), which drives white-to-brown fat conversion and hippocampal BDNF expression (PMID:23217713, PMID:25259918, PMID:22237023, PMID:32180561). Mutant huntingtin represses PPARGC1A transcription via CREB/TAF4 interference contributing to striatal neurodegeneration in Huntington's disease, while PARIS (ZNF746) accumulation in parkin-deficient neurons similarly silences PGC-1α to cause dopaminergic neuron loss relevant to Parkinson's disease (PMID:17018277, PMID:21376232).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    The foundational question of what couples cold exposure to mitochondrial thermogenesis in brown fat was answered by the cloning of PGC-1α as a cold-inducible PPARγ coactivator that activates UCP-1 and mitochondrial biogenesis in adipocytes.

    Evidence cDNA cloning from brown fat, retroviral overexpression in white adipocytes with UCP-1 induction and mitochondrial DNA quantification

    PMID:9529258

    Open questions at the time
    • Structural basis of PGC-1α–PPARγ interaction unresolved
    • In vivo loss-of-function not yet performed
  2. 1999 High

    How PGC-1α drives mitochondrial biogenesis beyond thermogenesis was established by demonstrating direct binding to and coactivation of NRF-1 on the mtTFA promoter, and by showing that PGC-1α's inherent activity depends on a conformational switch induced by nuclear receptor docking that enables recruitment of SRC-1 and CBP/p300.

    Evidence Co-IP and promoter reporter assays for NRF-1/mtTFA; GST pulldown and mammalian two-hybrid with domain mapping for SRC-1/CBP/p300 recruitment

    PMID:10412986 PMID:10558993

    Open questions at the time
    • Structural details of conformational switch not resolved
    • Whether all NR partners use the same activation mechanism unknown
  3. 2000 High

    PGC-1α's role in fatty acid oxidation was mechanistically grounded by mapping its LXXLL-motif-dependent, ligand-influenced interaction with PPARα and demonstrating functional enhancement of palmitate oxidation.

    Evidence GST pulldown, mammalian two-hybrid, domain deletion mutagenesis, palmitate oxidation assay in 3T3-L1 cells

    PMID:10669761

    Open questions at the time
    • Whether endogenous lipid ligands regulate PGC-1α–PPARα interaction in vivo not established
  4. 2001 High

    PGC-1α was placed at the center of fasting-induced hepatic gluconeogenesis: CREB directly induces PGC-1α transcription, and PGC-1α then coactivates PEPCK; separately, p38 MAPK phosphorylation was identified as a post-translational activation mechanism coupling cytokine/stress signals to PGC-1α stabilization and mitochondrial uncoupling.

    Evidence CREB KO mice with PGC-1α rescue for gluconeogenesis; kinase assays, phosphorylation mapping, and p38 inhibitors for phospho-activation

    PMID:11557984 PMID:11741533

    Open questions at the time
    • Specific p38 phosphorylation sites conferring stability vs. activity not fully dissected
    • Relative contribution of CREB vs. other promoter elements not quantified
  5. 2002 High

    The question of whether PGC-1α controls muscle fiber-type identity was resolved: transgenic expression drove type II-to-type I fiber conversion and fatigue resistance through cooperation with MEF2 and calcineurin signaling.

    Evidence MCK-PGC-1α transgenic mice with fiber-type analysis, electrical fatigue stimulation, calcineurin pathway experiments

    PMID:12181572

    Open questions at the time
    • Whether endogenous PGC-1α is necessary (not just sufficient) for fiber-type maintenance required KO confirmation
  6. 2004 High

    Global PGC-1α knockout resolved in vivo requirements: null mice confirmed defective hormone-stimulated gluconeogenesis in hepatocytes, revealed brain vulnerability (striatal lesions), and unexpectedly showed compensatory gluconeogenic gene expression via C/EBPβ.

    Evidence PGC-1α KO mouse with metabolic phenotyping, primary hepatocyte gluconeogenesis assays, brain histopathology

    PMID:15454086

    Open questions at the time
    • Mechanism of compensatory C/EBPβ activation not resolved
    • Tissue-specific contributions not disentangled by global KO
  7. 2005 High

    SIRT1 was identified as a direct deacetylase of PGC-1α, providing the NAD⁺-sensing mechanism that selectively channels PGC-1α activity toward gluconeogenic gene expression in fasting without activating mitochondrial targets.

    Evidence In vitro deacetylation with recombinant SIRT1, NAD⁺ dependence, reciprocal co-IP, point mutagenesis of SIRT1, hepatic gene expression analysis

    PMID:15716268 PMID:15744310

    Open questions at the time
    • How SIRT1 deacetylation selectively activates gluconeogenic but not mitochondrial programs mechanistically unexplained
    • Identity of the acetyltransferase counteracting SIRT1 on PGC-1α not established
  8. 2006 High

    Two disease-relevant regulatory axes were defined: PGC-1α partners with HNF4α to drive hepatic apolipoprotein/triglyceride output, and mutant huntingtin directly represses PGC-1α transcription via CREB/TAF4 interference, with PGC-1α deficiency exacerbating HD neurodegeneration and PGC-1α delivery providing neuroprotection.

    Evidence HNF4α response element mapping with adenoviral gain/loss-of-function for apolipoproteins; ChIP on PGC-1α promoter with PGC-1α KO × HD KI cross and lentiviral striatal rescue

    PMID:16574644 PMID:17018277

    Open questions at the time
    • Whether PGC-1α restoration is therapeutic in HD patients unknown
    • Relative contribution of HNF4α vs. other partners to hepatic lipid phenotype not quantified
  9. 2009 High

    Two inhibitory modifications were characterized: SUMOylation at K183 attenuates PGC-1α transactivation (potentially by recruiting corepressor RIP140), and DNMT3B-catalyzed non-CpG promoter methylation silences PGC-1α transcription in response to TNF-α and fatty acids, linking epigenetic repression to type 2 diabetes.

    Evidence SUMO conjugation assays with K183 mutagenesis and RIP140 co-IP; DNMT isoform-specific knockdown with bisulfite sequencing in human myotubes and diabetic tissue

    PMID:19625249 PMID:19723495

    Open questions at the time
    • Whether SUMOylation and acetylation at K183 are mutually exclusive in vivo not demonstrated
    • Causal role of DNMT3B methylation in diabetes pathogenesis not proven by genetic rescue
  10. 2010 High

    PGC-1α's target repertoire was expanded beyond mitochondria: it induces SIRT3 via ERRα to control ROS detoxification, drives peroxisomal biogenesis independently of PPARα, and regulates parvalbumin in GABAergic interneurons affecting cortical gamma-frequency processing.

    Evidence ChIP/EMSA for SIRT3 promoter ERRα element; PGC-1α KO with β-adrenergic stimulation and PPARα-null controls for peroxisomes; KO/overexpression with electrophysiology for parvalbumin

    PMID:20505089 PMID:20661474 PMID:21059926

    Open questions at the time
    • Whether peroxisomal function requires a distinct TF partner unknown
    • Mechanism linking PGC-1α to parvalbumin gene transcription not identified
  11. 2011 High

    The PARIS/parkin axis was established as a Parkinson's disease-relevant repressor of PGC-1α: PARIS binds insulin response sequences in the PGC-1α promoter, and its accumulation in parkin-deficient neurons suppresses PGC-1α, NRF-1, and dopaminergic neuron survival, rescued by PGC-1α coexpression.

    Evidence ChIP of PARIS on PGC-1α promoter, conditional parkin KO mice, PARIS overexpression with DA neuron counting, PGC-1α rescue

    PMID:21376232

    Open questions at the time
    • Whether PARIS repression is the primary mechanism of DA neuron loss in human PD not established
    • Additional parkin substrates converging on PGC-1α not excluded
  12. 2012 High

    Multiple breakthrough findings expanded PGC-1α biology: discovery of the myokine irisin (FNDC5) secreted downstream of muscle PGC-1α to induce browning and hippocampal BDNF; identification of PGC-1α4 isoform driving hypertrophy via IGF1/myostatin; genome-wide ChIP-seq defining combinatorial TF partnerships; IRF4 as an obligate thermogenic partner; and PGC-1α control of extrasynaptic NMDA receptor activity in neurons.

    Evidence Irisin: transgenic PGC-1α overexpression, FNDC5 secretion/cleavage, in vivo adenoviral elevation; PGC-1α4: alternative promoter characterization, transgenic muscle with mass/strength; ChIP-seq: genome-wide PGC-1α binding with NRF-1/ERRα/HNF4α co-occupancy; IRF4: co-IP, UCP1-Cre KO epistasis; NMDAR: electrophysiology with RNAi and mHtt epistasis

    PMID:22237023 PMID:22593067 PMID:22955979 PMID:23217713 PMID:24995979

    Open questions at the time
    • Irisin receptor identity not established at this time
    • Whether PGC-1α4 functions in human exercise-induced hypertrophy debated
    • HSF1 as novel PGC-1α partner from ChIP-seq not functionally validated
  13. 2013 High

    PGC-1α was implicated in cancer metabolism: MITF directly induces PGC-1α in melanoma upon BRAF inhibition, creating therapeutic dependence on mitochondrial respiration; separately, muscle PGC-1α was linked to hippocampal BDNF via the FNDC5/irisin pathway.

    Evidence BRAF inhibitor treatment with MITF knockdown/overexpression, PGC-1α promoter reporters, OCR; FNDC5 RNAi and overexpression in neurons, PGC-1α KO brain analysis, adenoviral peripheral FNDC5 delivery

    PMID:23477830 PMID:24120943

    Open questions at the time
    • Whether PGC-1α inhibition synergizes with BRAF inhibitors clinically untested
    • Whether peripheral irisin directly crosses the BBB or acts indirectly unknown
  14. 2014 High

    Tissue-specific PGC-1α functions were dissected: muscle PGC-1α1 upregulates kynurenine aminotransferases via PPARα/δ to protect against depression; endothelial PGC-1α induces Notch signaling causing diabetic-like vascular dysfunction; and PGC-1α drives mitochondrial oxidative phosphorylation specifically in invasive cancer cells to promote metastasis.

    Evidence Kynurenine: muscle-specific PGC-1α1 transgenic, KAT activity, plasma kynurenine, depression models; endothelial: tissue-specific KO/transgenic, wound healing, Notch/Akt/eNOS; metastasis: PGC-1α silencing with invasion assays and in vivo metastasis models

    PMID:24506866 PMID:25241037 PMID:25259918

    Open questions at the time
    • Whether muscle kynurenine clearance is quantitatively sufficient in humans unknown
    • Paradoxical pro- and anti-angiogenic roles of PGC-1α across endothelial vs. retinal contexts not reconciled
  15. 2017 High

    PGC-1α was found to localize to the nucleolus and promote ribosomal RNA transcription by recruiting RNA Pol I and UBF to rDNA—a function impaired in Huntington's disease—while functional interaction with Parkin was shown to coordinate mitochondrial biogenesis, quality control (Mfn2 turnover), and mitochondria-ER contacts for dopaminergic neuroprotection.

    Evidence Nucleolar fractionation with rDNA ChIP, human HD tissue; co-expression respirometry, Mfn2 transcription/degradation, in vivo DA neuron survival, ultrastructural ER-mitochondria analysis

    PMID:28053050 PMID:28819135

    Open questions at the time
    • Whether nucleolar PGC-1α function contributes to metabolic gene regulation or is an independent axis unclear
    • Structural basis of PGC-1α–Parkin cooperativity unknown
  16. 2019 High

    The PPARβ/δ–PGC-1α axis was shown to directly transactivate UCP3 via a distal PPRE in skeletal muscle, and UCP3 was demonstrated to be required for PGC-1α-induced oxidative capacity.

    Evidence ChIP-qPCR on UCP3 promoter PPRE, promoter deletion reporters, UCP3 siRNA with OCR measurements

    PMID:31228206

    Open questions at the time
    • Whether UCP3 functions as a bona fide uncoupler or a fatty acid transporter downstream of PGC-1α not resolved
  17. 2020 High

    PGC-1α was established as a driver of autophagy through SQSTM1/p62 regulation in vascular smooth muscle cells (preventing senescence), and isoform-specific hepatic functions were defined—PGC-1α1 for metabolism/inflammation, PGC-1α4 for anti-apoptotic protection.

    Evidence PGC-1α KO aortas with autophagy markers, SQSTM1 siRNA epistasis, TEM; primary hepatocyte isoform-specific adenoviral delivery with apoptosis assays

    PMID:31441382 PMID:32180561

    Open questions at the time
    • Direct transcriptional target linking PGC-1α to SQSTM1 not identified
    • Whether PGC-1α4 anti-apoptotic function operates in non-hepatic tissues unknown
  18. 2021 High

    Microglial PGC-1α was shown to promote mitophagy via ERRα-dependent ULK1 transcription, suppressing NLRP3 inflammasome activation after ischemic stroke; ULK1 knockdown abolished the neuroprotective effect.

    Evidence Microglia-specific PGC-1α transgenic mice, MCAO model, ChIP-Seq, ULK1 pharmacological and siRNA inhibition

    PMID:33771213

    Open questions at the time
    • Whether microglial PGC-1α has non-mitophagic anti-inflammatory mechanisms not excluded
    • Translation to human stroke not demonstrated
  19. 2023 Medium

    PGC-1α's regulatory scope was further expanded: it controls mitochondrial translation with ERRα in aging muscle (exercise-correctable), and in hepatocellular carcinoma it represses BAMBI/WNT signaling to regulate ferroptosis, with METTL3/WTAP-catalyzed m6A modification silencing PGC-1α mRNA under hypoxia.

    Evidence Aged mouse ribosome profiling with exercise; HCC gain/loss-of-function with patient organoids, m6A-seq, YTHDF2 pulldown, xenograft models

    PMID:36932115 PMID:37639610

    Open questions at the time
    • Mechanism by which PGC-1α/ERRα specifically controls mitochondrial (not cytoplasmic) translation not defined
    • m6A regulation of PGC-1α not confirmed outside HCC
    • BAMBI/ACSL5/ferroptosis axis awaits independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of PGC-1α's conformational activation by nuclear receptor docking; how distinct post-translational modifications (phosphorylation, deacetylation, SUMOylation, methylation) are integrated to select specific transcriptional outputs; and whether the nucleolar ribosomal biogenesis function is mechanistically separable from canonical metabolic coactivation.
  • No high-resolution structure of PGC-1α or PGC-1α–NR complex
  • Integrated PTM code not systematically tested
  • Nucleolar vs. nucleoplasmic functions not genetically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-9612973 Autophagy 2
Partners
CREBBPESRRAHNF4AIRF4NRF1PPARAPPARGSIRT1

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PGC-1α was identified as a cold-inducible transcriptional coactivator of nuclear receptors (PPARγ, thyroid hormone receptor) cloned from brown fat; ectopic expression in white adipocytes activated UCP-1 expression, key mitochondrial respiratory chain enzymes, and increased mitochondrial DNA content, establishing its role in adaptive thermogenesis. cDNA cloning, transient transfection reporter assays, retroviral overexpression in white adipocytes, mitochondrial DNA quantification Cell High 9529258
1999 PGC-1α stimulates mitochondrial biogenesis and respiration in muscle cells through induction of UCP-2 and regulation of NRF-1 and NRF-2 gene expression; PGC-1α directly binds to and coactivates NRF-1 on the mtTFA promoter, establishing a pathway linking external stimuli to mitochondrial biogenesis. Co-immunoprecipitation, promoter reporter assays (NRF-1/mtTFA), adenoviral overexpression in muscle cells, mitochondrial respiration measurements Cell High 10412986
1999 PGC-1α transcriptional activity is switched on by docking to PPARγ, which induces an apparent conformational change in PGC-1α permitting recruitment of histone acetyltransferases SRC-1 and CBP/p300 into an active complex; without transcription factor docking PGC-1α has low inherent activity. GST pulldown, co-immunoprecipitation, mammalian two-hybrid assays, transcriptional reporter assays with deletion mutants Science High 10558993
2000 PGC-1α coactivates PPARα in transcriptional control of mitochondrial fatty acid oxidation genes via an LXXLL motif in PGC-1α interacting with the PPARα AF2 region in a ligand-influenced manner; the transactivation domain maps to the N-terminal 120 amino acids, distinct from the PPARα-interacting domain. GST pulldown, mammalian two-hybrid, cotransfection reporter assays, retroviral expression in 3T3-L1 cells measuring palmitate oxidation, domain deletion mutagenesis Molecular and cellular biology High 10669761
2001 CREB directly regulates PGC-1α gene expression in liver in response to glucagon/fasting; PGC-1α then coactivates gluconeogenic gene expression (PEPCK), potentiating cooperativity between cAMP and glucocorticoid signaling pathways for hepatic gluconeogenesis. Targeted gene disruption (CREB KO mice), dominant-negative CREB overexpression, adenoviral PGC-1α rescue, transient transfection reporter assays Nature High 11557984
2001 Cytokines (IL-1α, IL-1β, TNFα) and LPS activate PGC-1α through phosphorylation by p38 MAP kinase, resulting in stabilization and activation of PGC-1α protein, which then increases mitochondrial uncoupling and energy expenditure in muscle cells. Kinase assays, phosphorylation site mapping, cotransfection, p38 inhibitors, oxygen consumption measurements in cultured muscle and in vivo Molecular cell High 11741533
2002 PGC-1α drives slow-twitch (type I) muscle fiber formation; transgenic expression at physiological levels converts type II fiber muscles to oxidative metabolism, induces type I fiber-specific proteins (troponin I slow, myoglobin), increases fatigue resistance, and acts through cooperation with Mef2 transcription factors and as a target of calcineurin signaling. Transgenic mouse generation (MCK-PGC-1α), fiber-type-specific promoter assays, electrical fatigue stimulation, gene expression analysis, calcineurin signaling experiments Nature High 12181572
2003 PGC-1α activates CYP7A1 gene transcription and bile acid biosynthesis in liver, functioning as a key link between fasting/diabetes and cholesterol-to-bile acid conversion. Adenoviral PGC-1α expression in HepG2 cells, transient transfection reporter assays on CYP7A1 promoter, bile acid biosynthesis measurement, streptozotocin diabetic mouse model The Journal of biological chemistry Medium 14522988
2004 PGC-1α null mice demonstrate that hepatocytes lacking PGC-1α are defective in hormone-stimulated gluconeogenesis, but have constitutively active gluconeogenic gene expression driven by elevated C/EBPβ in a PGC-1α-independent manner; null mice are lean and hyperactive with striatal brain lesions, revealing PGC-1α's role in brain energy homeostasis. PGC-1α knockout mouse generation, hepatocyte primary culture, gluconeogenesis assays, brain histopathology, metabolic phenotyping Cell High 15454086
2005 SIRT1 directly interacts with and deacetylates PGC-1α at specific lysine residues in an NAD+-dependent manner in response to fasting/pyruvate signals; SIRT1 induces gluconeogenic genes and hepatic glucose output through PGC-1α but does not regulate PGC-1α's mitochondrial gene targets; PGC-1α is acetylated in vivo. Co-immunoprecipitation, in vitro deacetylation assay with recombinant SIRT1, NAD+-dependence testing, adenoviral knockdown/overexpression in liver, gluconeogenesis gene expression analysis Nature High 15744310
2005 SIRT1 directly interacts with PGC-1α and can be co-immunoprecipitated as a complex; SIRT1 alters PGC-1α transcriptional activity; a single amino acid mutation in the SIRT1 ADP-ribosyltransferase domain abolishes interaction with PGC-1α but not p53 or Foxo3a; PGC-1α is acetylated in vivo and SIRT1 catalyzes its deacetylation both in vitro and in vivo. Co-immunoprecipitation, in vitro deacetylation assay, SIRT1 point mutagenesis, oxygen consumption measurements in PC12 cells The Journal of biological chemistry High 15716268
2006 PGC-1α partners with HNF4α in the fasted liver to specifically activate apolipoprotein genes (ApoA-IV, ApoC-II, ApoC-III) through a conserved HNF4α response element; adenoviral PGC-1α in vivo increases hepatic apolipoprotein expression and serum/VLDL triglyceride levels; knockdown reduces both apolipoprotein expression and serum triglycerides. Cotransfection reporter assays with HNF4α response element mutations, adenoviral in vivo delivery, siRNA knockdown, serum triglyceride measurement The Journal of biological chemistry High 16574644
2006 Mutant huntingtin represses PGC-1α gene transcription by associating with the PGC-1α promoter and interfering with CREB/TAF4-dependent transcriptional activation; PGC-1α deficiency exacerbates striatal neurodegeneration in HD knockin mice, while PGC-1α expression partially reverses mutant huntingtin toxicity; lentiviral delivery of PGC-1α to striatum is neuroprotective in transgenic HD mice. Chromatin immunoprecipitation (PGC-1α promoter), PGC-1α KO × HD KI crossbreeding, lentiviral striatal delivery, cultured striatal neuron assays Cell High 17018277
2009 SUMOylation of PGC-1α at lysine 183 (in the activation domain) attenuates its transcriptional activity, likely by enhancing interaction with corepressor RIP140; SUMOylation does not affect subcellular localization or stability of PGC-1α; the same lysine is also targeted for acetylation, indicating competitive modification at this site. SUMO conjugation assays, site-directed mutagenesis (K183, E185A), co-immunoprecipitation with RIP140, transcriptional reporter assays for PPARγ-dependent and general coactivation The Journal of biological chemistry High 19625249
2009 Non-CpG methylation of the PGC-1α promoter by DNMT3B (but not DNMT1 or DNMT3A) controls mitochondrial density; TNF-α and free fatty acids acutely increase non-CpG methylation in human myotubes; PGC-1α promoter hypermethylation correlates with reduced PGC-1α mRNA and mitochondrial DNA in type 2 diabetic subjects. Whole-genome promoter methylation analysis, bisulfite sequencing, selective DNMT siRNA knockdown, human myotube culture with fatty acid treatment, mtDNA quantification Cell metabolism High 19723495
2010 PGC-1α transcriptionally induces SIRT3 expression through an estrogen-related receptor alpha (ERRα) binding element in the SIRT3 promoter; SIRT3 mediates PGC-1α-dependent induction of ROS-detoxifying enzymes (GPx-1, SOD2) and respiratory chain components; SIRT3 knockdown increases cellular ROS and blocks the inhibitory effect of PGC-1α on ROS production and mitochondrial biogenesis. Promoter reporter assays, EMSA, chromatin immunoprecipitation, siRNA knockdown of ERRα and SIRT3, ROS measurements, mitochondrial biogenesis assays in C2C12 myotubes PloS one High 20661474
2010 PGC-1α promotes peroxisomal remodeling and biogenesis in addition to mitochondrial biogenesis; ectopic PGC-1α expression recapitulates thermogenic stimulus-induced peroxisome expansion in vitro and in vivo; this peroxisomal function is independent of PPARα, establishing PGC-1α as a broad orchestrator of organelle adaptation to energy demands. PGC-1α knockout cells with β-adrenergic stimulation, ectopic PGC-1α expression in vitro and in vivo, peroxisomal marker analysis, PPARα null cells Proceedings of the National Academy of Sciences of the United States of America High 21059926
2010 PGC-1α regulates parvalbumin expression in GABAergic interneurons; PGC-1α knockout mice show striking reduction in parvalbumin expression throughout the cerebrum, while PGC-1α overexpression in cell culture robustly induces parvalbumin; loss of parvalbumin leads to altered synaptic facilitation during gamma-frequency stimulation without loss of PV-expressing interneurons. PGC-1α KO mouse analysis, cell culture overexpression, electrophysiology (paired-pulse and gamma-frequency stimulation), immunohistochemistry, gene expression analysis across multiple tissues The Journal of neuroscience High 20505089
2011 PARIS (ZNF746), a parkin substrate regulated by parkin-mediated ubiquitination, represses PGC-1α gene expression by binding to insulin response sequences in the PGC-1α promoter; PARIS accumulation in parkin-deficient neurons leads to PGC-1α repression, reduced NRF-1 expression, and progressive dopaminergic neuron loss that is rescued by PGC-1α coexpression. ChIP (PARIS binding to PGC-1α promoter), conditional parkin KO mice, PARIS overexpression with dopaminergic neuron counting, PGC-1α rescue by coexpression, ubiquitination assays Cell High 21376232
2011 ATGL-mediated lipolysis generates lipid ligands that activate PPARα/δ, which in turn maintains PGC-1α and PGC-1β expression in the heart; ATGL deficiency in mice decreases PGC-1α/β expression, causing disrupted mitochondrial substrate oxidation and lethal cardiomyopathy that is completely reversed by pharmacological PPARα agonist treatment. Tissue-specific ATGL knockout mice, PPARα agonist pharmacological rescue, mitochondrial respiration assays, gene expression analysis Nature medicine High 21857651
2012 PGC-1α expression in skeletal muscle stimulates expression of FNDC5 (a membrane protein cleaved and secreted as irisin); irisin acts on white adipose cells to stimulate UCP1 expression and brown-fat-like development; mildly elevated irisin in blood increases energy expenditure in mice without changing food intake or movement. Transgenic muscle-specific PGC-1α overexpression, FNDC5 cloning and secretion analysis, in vitro white adipocyte treatment, adenoviral irisin elevation in vivo, indirect calorimetry Nature High 22237023
2012 IRF4 is a transcriptional partner of PGC-1α in adipocytes for thermogenic gene expression; IRF4 physically interacts with PGC-1α and both drive Ucp1 expression; IRF4 KO in UCP1+ cells reduces thermogenesis and causes obesity; cold, β-agonists, or forced PGC-1α expression cannot induce thermogenic gene expression in the absence of IRF4. Co-immunoprecipitation of IRF4 and PGC-1α, UCP1-Cre-specific IRF4 KO mice, IRF4 transgenic overexpression, Ucp1 reporter assays, metabolic phenotyping, gene expression profiling Cell High 24995979
2012 PGC-1α induces VEGFA expression in retinal cells and is required for normal retinal vascular development; PGC-1α knockout mice have reduced retinal vascular outgrowth and capillary density; in oxygen-induced retinopathy, PGC-1α drives pathological neovascularization and PGC-1α KO mice are protected from pathological vessel growth. PGC-1α KO mouse retinal vascular analysis, oxygen-induced retinopathy model, VEGFA expression assays, retinal vascular morphometry The American journal of pathology High 23141926
2012 A genome-wide PPARGC1A binding map in HepG2 cells (ChIP-seq) reveals extensive co-binding with NRF-1, ERRα, HNF4α, and a novel link to HSF1; different TF combinations bind distinct functional gene sets, revealing the combinatorial regulatory code underlying PGC-1α-driven metabolic gene expression. ChIP-seq for PPARGC1A and six transcription factor partners, motif analysis, combinatorial binding analysis Genome research High 22955979
2012 PGC-1α controls extrasynaptic NMDA receptor (NMDAR_EX) activity in neurons; PGC-1α knockdown increases NMDAR_EX currents and vulnerability to excitotoxicity; mutant huntingtin suppresses PGC-1α and increases NMDAR_EX activity through a common mechanism, as their effects are nonadditive and exogenous PGC-1α rescues mHtt-induced NMDAR_EX upregulation and excitotoxic death. Electrophysiology (extrasynaptic vs. synaptic NMDAR currents), RNAi knockdown, mHtt expression (148Q vs. 18Q), exogenous PGC-1α rescue in rat cortical and striatal neurons, NMDA excitotoxicity assay The Journal of neuroscience High 22593067
2012 A novel PGC-1α isoform (PGC-1α4), arising from alternative promoter usage and splicing, is highly expressed in resistance-exercised muscle and does not regulate mitochondrial OXPHOS genes; instead, PGC-1α4 specifically induces IGF1 and represses myostatin, driving robust skeletal muscle hypertrophy both in vitro and in vivo. Alternative promoter/splicing characterization, transgenic skeletal muscle PGC-1α4 overexpression, muscle mass and strength measurements, cancer cachexia model, IGF1/myostatin expression analysis, exercise induction in mouse and human muscle biopsies Cell High 23217713
2013 Oncogenic BRAF inhibition induces PGC1α expression in melanoma via the MITF transcription factor, which directly regulates PGC1α; BRAF/MAPK pathway activation suppresses MITF and PGC1α levels and decreases oxidative metabolism; BRAF inhibitor treatment renders melanoma cells dependent on mitochondrial respiration driven by PGC1α. BRAF inhibitor treatment, MITF knockdown and overexpression, PGC1α promoter reporter assays, oxygen consumption rate measurements, gene expression profiling Cancer cell High 23477830
2013 PGC-1α and FNDC5 mediate exercise-induced BDNF expression in the hippocampus; neuronal Fndc5 is regulated by PGC-1α; Pgc1a knockout mice show reduced Fndc5 in the brain; forced FNDC5 expression increases Bdnf, while FNDC5 RNAi reduces it; peripheral delivery of FNDC5 via adenoviral vectors elevates blood irisin and induces BDNF in the hippocampus. PGC-1α KO mice, RNAi knockdown of FNDC5, forced FNDC5 expression in primary cortical neurons, adenoviral peripheral delivery of FNDC5, hippocampal gene expression Cell metabolism High 24120943
2014 Endothelial PGC-1α induces Notch signaling, blunts Rac/Akt/eNOS activation, and renders endothelial cells unresponsive to angiogenic factors; transgenic endothelial PGC-1α overexpression mimics diabetic vascular phenotypes; endothelial PGC-1α deletion rescues blunted wound healing and ischemic recovery in type 1 and type 2 diabetic mice. Endothelial-specific PGC-1α transgenic and KO mice, carotid injury re-endothelialization, hindlimb ischemia model, wound healing assay, Notch/Akt/eNOS signaling analysis Cell metabolism High 24506866
2014 PGC-1α mediates mitochondrial biogenesis and increased oxidative phosphorylation specifically in invasive/migratory cancer cells; silencing PGC-1α suspends invasive potential and attenuates metastasis without affecting proliferation or primary tumor growth; PGC-1α expression in human invasive breast cancers correlates with distant metastasis. PGC-1α silencing in cancer cells, invasion/migration assays, oxygen consumption rate measurement, in vivo metastasis models, human breast cancer tissue analysis Nature cell biology High 25241037
2014 Skeletal muscle PGC-1α1 activates the PPARα/δ pathway to upregulate kynurenine aminotransferases, enhancing conversion of kynurenine to kynurenic acid (which cannot cross the blood-brain barrier), thereby reducing plasma kynurenine and protecting against stress-induced depression in mice. Skeletal muscle-specific PGC-1α1 transgenic mice, kynurenine aminotransferase expression and activity assays, plasma kynurenine/kynurenic acid measurement, chronic mild stress and direct kynurenine administration depression models, PPARα/δ transcriptional assays Cell High 25259918
2014 Endothelial PGC-1α promotes eNOS expression through the orphan nuclear receptor ERRα; endothelial-specific PGC-1α KO sensitizes to ATII-induced endothelial dysfunction and hypertension; PGC-1α transgenic mice are protected; eNOS inhibition (LNAME) or eNOS KO abolishes the protective effect, placing eNOS downstream of ERRα/PGC-1α. Endothelial-specific PGC-1α KO and transgenic mice, ATII-induced hypertension, eNOS inhibitor (LNAME), eNOS KO epistasis, eNOS expression analysis Scientific reports High 27910955
2014 The protease Omi cleaves GSK3β, a kinase that promotes PGC-1α degradation; loss of Omi increases GSK3β abundance and decreases PGC-1α, causing mitochondrial biogenesis deficits and neurodegeneration; GSK3β inhibition or PGC-1α overexpression restores mitochondrial biogenesis and improves movement in mnd2 mice. mnd2 mouse model (Omi-deficient), GSK3β inhibitor SB216763, PGC-1α overexpression, mitochondrial density quantification, mtDNA copy number, movement assays Cell death & disease Medium 25118933
2016 PGC-1α interacts with ERRα and recruits it to an ERRα response element in the proximal MPC1 promoter, directly activating mitochondrial pyruvate carrier 1 (MPC1) transcription; MPC1 is required for PGC-1α-induced pyruvate-dependent mitochondrial oxygen consumption. PGC-1α siRNA, ERRα ChIP, MPC1 promoter reporter assay, PGC-1α overexpression, UK5099 MPC inhibitor, oxygen consumption rate measurement The Biochemical journal High 29669911
2016 PGC-1α promotes ureagenesis in periportal hepatocytes by upregulating SIRT3 and SIRT5, which deacetylate and activate the urea cycle enzymes OTC and CPS1, respectively; PGC-1α null mice show significantly reduced 15N-labeled urea production from labeled alanine. PGC-1α null mice, 15N/13C isotope tracing in perfused liver, PGC-1α overexpression, SIRT3/SIRT5 expression analysis, CPS1 and OTC activity assays, deacetylation assays Scientific reports High 27052737
2017 A fraction of cellular PGC-1α localizes to the nucleolus and associates with ribosomal DNA upon activation, boosting RNA polymerase I and UBF recruitment to the rDNA promoter and inducing ribosomal RNA transcription; this nucleolar function is impaired in early human Huntington's disease. Nucleolar fractionation, ChIP on rDNA promoter (RNA Pol I, UBF, PGC-1α), cell culture activation models, mouse models, human HD tissue analysis Scientific reports High 28819135
2017 Parkin and PGC-1α functionally interact: Parkin controls PGC-1α transcription, and co-expression increases mitochondrial number, enhances maximal respiration, accelerates mitochondrial membrane potential recovery; PGC-1α enhances Mfn2 transcription but also increases Mfn2 protein degradation via Parkin; in vivo co-expression of both provides neuroprotection to substantia nigra dopaminergic neurons and controls mitochondria-ER interaction density. Cortical neuron co-expression, respirometry, mitochondrial membrane potential assay, Mfn2 transcription and protein stability assays, in vivo dopaminergic neuron survival counts, ultrastructural analysis Human molecular genetics High 28053050
2018 Mutant p53 (gain-of-function) binds and regulates PGC-1α to enhance mitochondrial function and metastatic capability; this regulation depends on the codon 72 polymorphism (R72 variant of mutant p53 shows greater PGC-1α function); breast cancers with mutant p53 and the R72 variant have poorer prognosis. Co-immunoprecipitation of mutant p53 with PGC-1α, migration/invasion assays, mitochondrial function measurements, in vivo metastasis, human cancer tissue prognosis analysis Genes & development Medium 29463573
2019 PGC-1α/PPARβ axis drives Ucp3 gene expression in skeletal muscle cells via transactivation of a distal PPAR response element in the Ucp3 promoter; this mechanism operates during myogenesis and during fatty acid-induced metabolic stress; Ucp3 is essential for PGC-1α-induced oxidative capacity. ChIP-qPCR on Ucp3 promoter PPRE, promoter deletion reporter assays, siRNA knockdown of UCP3, oxygen consumption rate measurements, fatty acid treatment models The Journal of physiology High 31228206
2020 PPARGC1A upregulates autophagy and reduces vascular smooth muscle cell senescence through a SQSTM1/p62-dependent mechanism; PPARGC1A-deficient VSMCs show reduced autophagosome number, reduced LC3-II, and reduced SQSTM1, while PPARGC1A overexpression upregulates SQSTM1; SQSTM1 siRNA mimics the ppargc1a KO phenotype of reduced autophagy and increased senescence in vitro and in vivo. PPARGC1A KO mouse aorta analysis, siRNA knockdown, autophagy inhibitors (3-MA, spautin-1, Atg5 siRNA), rapamycin rescue, senescence assays (SA-β-gal), transmission electron microscopy of autophagosomes Autophagy High 31441382
2020 PGC-1α isoforms have distinct hepatic functions: PGC-1α1 primarily regulates nutrient metabolism and mitochondrial gene programs, while PGC-1α4 uniquely enhances anti-apoptotic gene expression and attenuates hepatocyte apoptosis in response to TNFα/LPS; PGC-1α1 reduces inflammatory gene networks but does not prevent cytokine-induced hepatocyte death. Primary mouse hepatocyte isoform-specific gain- and loss-of-function (adenoviral delivery), microarray gene expression, caspase-3 and apoptosis assays, TNFα/LPS treatment, in vivo isoform-specific mouse models Molecular metabolism High 32180561
2020 ppargc1a is essential for ciliogenesis in zebrafish, performing this function through prostaglandin signaling; ppargc1a specifically reduces ptgs1 (prostaglandin-endoperoxide synthase 1) expression; PGE2 treatment rescues cilia defects and renal multiciliated cell fate in ppargc1a-deficient embryos; ptgs1 overexpression also rescues the ppargc1a morphant phenotype. Zebrafish morpholino knockdown and mutant analysis, PGE2 rescue, ptgs1 overexpression rescue, renal tubule cell fate analysis, cilia imaging Cell reports Medium 33176142
2021 Microglial PGC-1α promotes autophagy and mitophagy through interaction with ERRα to drive ULK1 expression; microglial PGC-1α overexpression after ischemic stroke reduces NLRP3 activation and proinflammatory cytokine production; pharmacological or genomic ULK1 inhibition abolishes the neuroprotective and mitophagic effects of PGC-1α. Microglia-specific PGC-1α transgenic mice, MCAO stroke model, ChIP-Seq (PGC-1α binding sites in microglia), ULK1 pharmacological inhibition and siRNA knockdown, immunofluorescence of autolysosomes, NLRP3/cytokine assays Genome medicine High 33771213
2021 PGC-1α/PPAR signaling controls multiple aspects of cardiomyocyte maturation simultaneously through YAP1 and SF3B2 as previously unrecognized effectors; this signaling is active in vivo but inactive in pluripotent stem cell-derived cardiomyocytes; mosaic gene deletion confirmed PGC-1α as the driver of the transcriptomic maturation shift. Large-particle sorting of single postnatal/adult cardiomyocytes, single-cell transcriptomics, gene regulatory network analysis, mosaic gene deletion Nature communications Medium 33712605
2023 PGC-1α and ERRα regulate mitochondrial translation in skeletal muscle; age-related sarcopenia is associated with a robust mitochondrial translation impairment; exercise activates PGC-1α and rectifies age-related reduction in mitochondrial translation in conjunction with quality control pathways. Aged mouse skeletal muscle analysis, PGC-1α activity manipulation, mitochondrial ribosome profiling/translation assays, ERRα interaction studies, exercise intervention Proceedings of the National Academy of Sciences of the United States of America Medium 37639610
2023 PPARGC1A represses BAMBI by inhibiting WNT/β-catenin signaling; BAMBI regulates ACSL5 through TGF-β/SMAD signaling; the PPARGC1A/BAMBI/ACSL5 axis controls ROS production and ferroptosis-related cell death in hepatocellular carcinoma; METTL3/WTAP silence PPARGC1A via m6A-YTHDF2-dependent mRNA modification under hypoxia. Gain- and loss-of-function in HCC cell lines, patient-derived organoids, mouse xenograft models; WNT/β-catenin and TGF-β/SMAD pathway analysis; m6A-seq and YTHDF2 pulldown; metformin rescue of m6A modification Oncogene Medium 36932115

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 3739 22237023
1999 Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 3388 10412986
1998 A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 3148 9529258
2005 Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2626 15744310
2002 Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2132 12181572
2003 Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine reviews 1695 12588810
2003 Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences of the United States of America 1614 12832613
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current opinion in lipidology 1317 19276888
2001 CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 1181 11557984
2014 PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nature cell biology 1154 25241037
2013 Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell metabolism 1069 24120943
2010 Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochimica et biophysica acta 1021 20933024
2011 Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. The American journal of clinical nutrition 1019 21289221
2004 Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 1000 15454086
2006 PGC-1alpha: a key regulator of energy metabolism. Advances in physiology education 993 17108241
2008 AMPK and PPARdelta agonists are exercise mimetics. Cell 977 18674809
2000 The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and cellular biology 968 10669761
2006 Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocrine reviews 943 17018837
2005 SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. The Journal of biological chemistry 894 15716268
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2006 Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 827 17018277
2011 PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease. Cell 810 21376232
2013 Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer cell 722 23477830
2003 Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. The Journal of physiology 713 12563009
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nature medicine 641 21857651
2013 PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer cell 612 23416000
2001 Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Molecular cell 608 11741533
2014 Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 604 25259918
2010 Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PloS one 604 20661474
2015 MYC/PGC-1α Balance Determines the Metabolic Phenotype and Plasticity of Pancreatic Cancer Stem Cells. Cell metabolism 600 26365176
2016 Sirt1 and the Mitochondria. Molecules and cells 597 26831453
2012 A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 542 23217713
2012 PGC1α and mitochondrial metabolism--emerging concepts and relevance in ageing and neurodegenerative disorders. Journal of cell science 493 23277535
1999 Activation of PPARgamma coactivator-1 through transcription factor docking. Science (New York, N.Y.) 492 10558993
2009 Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell metabolism 482 19723495
2011 A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. Cancer cell 460 22094256
2018 PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation. International journal of molecular sciences 371 30400212
2011 Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia. International journal of molecular sciences 285 22072942
2014 IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 263 24995979
2009 PGC-1{alpha} and PGC-1{beta} regulate mitochondrial density in neurons. The Journal of biological chemistry 253 19542216
2005 Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-alpha. International journal of obesity (2005) 232 15711583
2020 The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases. Biomolecules 225 32102312
2013 Regulation of mitochondrial biogenesis and PGC-1α under cellular stress. Mitochondrion 218 23347985
2008 PGC-1 coactivators and skeletal muscle adaptations in health and disease. Current opinion in genetics & development 190 18782618
2019 Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators. Nature reviews. Gastroenterology & hepatology 182 30518830
2013 PGC-1α, mitochondrial dysfunction, and Huntington's disease. Free radical biology & medicine 181 23602910
2021 Microglial PGC-1α protects against ischemic brain injury by suppressing neuroinflammation. Genome medicine 170 33771213
2019 SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. Autophagy 152 31441382
2019 The metabolic modulator PGC-1α in cancer. American journal of cancer research 142 30906622
2014 Endothelial PGC-1α mediates vascular dysfunction in diabetes. Cell metabolism 140 24506866
2014 PPARγ and PGC-1α as therapeutic targets in Parkinson's. Neurochemical research 140 25007880
2013 Pre-diabetes alters testicular PGC1-α/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress. Biochimica et biophysica acta 125 24361842
2014 The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy. Autophagy 104 24598403
2016 PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: Role of epoxyeicosatrienoic acid. Prostaglandins & other lipid mediators 98 27418542
2009 The biology of PGC-1α and its therapeutic potential. Trends in pharmacological sciences 96 19446346
2012 PGC-1 proteins and heart failure. Trends in cardiovascular medicine 95 22939990
2010 Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis. Proceedings of the National Academy of Sciences of the United States of America 94 21059926
2004 PGC-1alpha: turbocharging mitochondria. Cell 94 15454076
2010 Parvalbumin deficiency and GABAergic dysfunction in mice lacking PGC-1alpha. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 20505089
2018 Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α. Genes & development 91 29463573
2009 SUMOylation attenuates the function of PGC-1alpha. The Journal of biological chemistry 91 19625249
2000 Regulation of adipogenesis and energy balance by PPARgamma and PGC-1. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 89 11126248
2003 PGC-1alpha activates CYP7A1 and bile acid biosynthesis. The Journal of biological chemistry 88 14522988
2016 PGC-1α Induces Human RPE Oxidative Metabolism and Antioxidant Capacity. Investigative ophthalmology & visual science 86 26962700
2016 Role of PGC-1α in Vascular Regulation: Implications for Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 84 27312223
2008 Minireview: the PGC-1 coactivator networks: chromatin-remodeling and mitochondrial energy metabolism. Molecular endocrinology (Baltimore, Md.) 84 19008463
2018 MiR-494-3p regulates mitochondrial biogenesis and thermogenesis through PGC1-α signalling in beige adipocytes. Scientific reports 82 30305668
2021 PGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2. Nature communications 78 33712605
2020 Natural products, PGC-1 , and Duchenne muscular dystrophy. Acta pharmaceutica Sinica. B 78 32528825
2022 SnapShot: Regulation and biology of PGC-1α. Cell 77 35427500
2023 Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma. Oncogene 76 36932115
2019 Melatonin/PGC1A/UCP1 promotes tumor slimming and represses tumor progression by initiating autophagy and lipid browning. Journal of pineal research 75 31469445
2017 Parkin functionally interacts with PGC-1α to preserve mitochondria and protect dopaminergic neurons. Human molecular genetics 75 28053050
2016 The association between PGC-1α and Alzheimer's disease. Anatomy & cell biology 75 27051562
2014 SIRT3 protects cells from hypoxia via PGC-1α- and MnSOD-dependent pathways. Neuroscience 71 25433241
2006 Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism. The Journal of biological chemistry 71 16574644
2007 Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure. Diabetologia 70 17828388
2018 Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation. Cardiovascular research 67 29931197
2012 A highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells. Genome research 66 22955979
2012 PGC-1α regulates normal and pathological angiogenesis in the retina. The American journal of pathology 64 23141926
2021 Synergistic cardioptotection by tilianin and syringin in diabetic cardiomyopathy involves interaction of TLR4/NF-κB/NLRP3 and PGC1a/SIRT3 pathways. International immunopharmacology 63 33971494
2010 The role of PGC-1α in the pathogenesis of neurodegenerative disorders. Current drug targets 62 20840068
2020 Multiple Levels of PGC-1α Dysregulation in Heart Failure. Frontiers in cardiovascular medicine 60 32083094
2011 The PPARGC1A gene Gly482Ser in Polish and Russian athletes. Journal of sports sciences 59 22122487
2011 Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver. American journal of physiology. Regulatory, integrative and comparative physiology 58 21832205
2003 Differential expression of Akt, PPARgamma, and PGC-1 during hibernation in bats. Biochemistry and cell biology = Biochimie et biologie cellulaire 58 14569299
2009 Do PPARGC1A and PPARalpha polymorphisms influence sprint or endurance phenotypes? Scandinavian journal of medicine & science in sports 56 19422653
2012 PGC-1α negatively regulates extrasynaptic NMDAR activity and excitotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 22593067
2013 Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology. Seminars in immunopathology 51 24258516
2006 Gluconeogenesis: re-evaluating the FOXO1-PGC-1alpha connection. Nature 51 17024043
2020 Functional effects of muscle PGC-1alpha in aged animals. Skeletal muscle 50 32375875
2014 The protease Omi regulates mitochondrial biogenesis through the GSK3β/PGC-1α pathway. Cell death & disease 50 25118933
2015 Overexpression of PGC-1α Influences Mitochondrial Signal Transduction of Dopaminergic Neurons. Molecular neurobiology 49 26141122
2014 The role of nNOS and PGC-1α in skeletal muscle cells. Journal of cell science 49 25217629
2016 SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway. Endocrine 46 27022940
2019 Posttranslational regulation of PGC-1α and its implication in cancer metabolism. International journal of cancer 45 30848477
2016 Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway. Biochimica et biophysica acta. General subjects 45 27793739
2016 PGC-1α dictates endothelial function through regulation of eNOS expression. Scientific reports 44 27910955
2019 Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration. Life science alliance 43 31101737
2020 Exercise enhances mitochondrial fission and mitophagy to improve myopathy following critical limb ischemia in elderly mice via the PGC1a/FNDC5/irisin pathway. Skeletal muscle 42 32933582
2020 Resveratrol protects mitochondrial quantity by activating SIRT1/PGC-1α expression during ovarian hypoxia. Reproductive medicine and biology 40 32273826
2019 Apolipoprotein E regulates mitochondrial function through the PGC-1α-sirtuin 3 pathway. Aging 39 31808750
2017 Role of microRNA-130b in placental PGC-1α/TFAM mitochondrial biogenesis pathway. Biochemical and biophysical research communications 39 28433632
2019 Role of PGC-1α in Mitochondrial Quality Control in Neurodegenerative Diseases. Neurochemical research 38 31410709
2010 Modular evolution of PGC-1alpha in vertebrates. Journal of molecular evolution 38 20443112
2016 Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway. Scientific reports 37 27098390
2020 PGC-1α isoforms coordinate to balance hepatic metabolism and apoptosis in inflammatory environments. Molecular metabolism 36 32180561
2021 Covering the Role of PGC-1α in the Nervous System. Cells 35 35011673
2018 Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway. Biochemical and biophysical research communications 35 30172371
2017 Ribosomal transcription is regulated by PGC-1alpha and disturbed in Huntington's disease. Scientific reports 35 28819135
2011 The PGC-1α-related coactivator promotes mitochondrial and myogenic adaptations in C2C12 myotubes. American journal of physiology. Regulatory, integrative and comparative physiology 35 21795630
2020 PGC-1α regulates autophagy to promote fibroblast activation and tissue fibrosis. Annals of the rheumatic diseases 34 32482644
2018 MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis. The Biochemical journal 34 29669911
2016 PGC-1α Promotes Ureagenesis in Mouse Periportal Hepatocytes through SIRT3 and SIRT5 in Response to Glucagon. Scientific reports 34 27052737
2015 Regulation of PGC-1α Isoform Expression in Skeletal Muscles. Acta naturae 32 25927001
2021 PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia. Mitochondrion 30 33812061
2021 Role of PGC-1α in the Mitochondrial NAD+ Pool in Metabolic Diseases. International journal of molecular sciences 30 33925372
2017 PPARGC1A is upregulated and facilitates lung cancer metastasis. Experimental cell research 30 28803067
2023 Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α. Proceedings of the National Academy of Sciences of the United States of America 29 37639610
2013 FoxO6 and PGC-1α form a regulatory loop in myogenic cells. Bioscience reports 29 23639108
2009 Is there an interaction between PPARD T294C and PPARGC1A Gly482Ser polymorphisms and human endurance performance? Experimental physiology 29 19666693
2006 The Gly482Ser variant of the PPARGC1 gene is associated with Type 2 diabetes mellitus in northern Chinese, especially men. Diabetic medicine : a journal of the British Diabetic Association 29 16978372
2018 Deciphering the Dichotomous Effects of PGC-1α on Tumorigenesis and Metastasis. Frontiers in oncology 28 29629336
2021 Flavonoids modulate AMPK/PGC-1α and interconnected pathways toward potential neuroprotective activities. Metabolic brain disease 27 33988807
2020 Ppargc1a Controls Ciliated Cell Development by Regulating Prostaglandin Biosynthesis. Cell reports 27 33176142
2019 Essential role of the PGC-1α/PPARβ axis in Ucp3 gene induction. The Journal of physiology 27 31228206
2015 Dihydromyricetin stimulates irisin secretion partially via the PGC-1α pathway. Molecular and cellular endocrinology 26 26054747