| 2013 |
PERM1 (Perm1) acts downstream of PGC-1α and ERRs in skeletal muscle to regulate expression of selective PGC-1/ERR target genes involved in glucose and lipid metabolism, energy transfer, and contractile function; silencing Perm1 in myotubes reduces respiratory capacity and diminishes PGC-1α-induced mitochondrial biogenesis. |
siRNA knockdown in cultured myotubes, respiratory capacity assays, gene expression analysis; genetic epistasis placing Perm1 downstream of PGC-1α/ERR |
The Journal of biological chemistry |
Medium |
23836911
|
| 2015 |
AAV1-mediated overexpression of Perm1 in adult mouse skeletal muscle in vivo increases mitochondrial content and oxidative capacity by 40–80%, increases capillary density, and increases fatigue resistance by ~31–33%, without prominent fiber-type composition changes. |
AAV1-mediated gene delivery in mice, mitochondrial content quantification, oxidative capacity assays, capillary density measurement, fatigue testing |
FASEB journal |
High |
26481306
|
| 2019 |
Perm1 physically associates with CaMKII in skeletal muscle and promotes CaMKII activation; knockdown of Perm1 in mouse gastrocnemius via AAV-shRNA blunts exercise-induced CaMKII and p38 MAPK activation, reduces induction of oxidative metabolism regulators after acute exercise, and attenuates mitochondrial biogenesis after four weeks of voluntary training. |
Immunoprecipitation and mass spectrometry to identify Perm1-associated proteins; validated interaction with CaMKII; AAV-shRNA knockdown in vivo; treadmill exercise and voluntary wheel running with molecular readouts |
Molecular metabolism |
High |
30862473
|
| 2020 |
Smyd1 (histone methyltransferase) directly occupies the Perm1 promoter in mouse heart, and Perm1 acts downstream of Smyd1 to regulate cardiac energetics; Perm1 overexpression rescues phenylephrine-induced downregulation of ERRα and its target Ndufv1 (Complex I); Perm1 dose-dependently activates the ERRα promoter and the ERRα target Ndufv1; siRNA knockdown of Perm1 reduces basal respiration and ATP production in cardiomyocytes. |
ChIP assay (Smyd1 at Perm1 promoter), adenovirus-mediated Perm1 overexpression, siRNA knockdown, Seahorse XF respiration assay, luciferase reporter gene assay |
PloS one |
High |
32574189
|
| 2020 |
ESRRG and PERM1 are induced early during cold-mediated brite/beige adipocyte formation and positively regulate mitochondrial capacity within the PGC-1α transcriptional network; increased expression of PERM1 supports brite/beige adipocyte formation in vitro and in vivo. |
Transcriptome profiling of inguinal adipocytes during cold exposure, gain-of-function overexpression in vitro and in vivo, mitochondrial capacity assays |
Frontiers in endocrinology |
Medium |
32595605
|
| 2021 |
PERM1 interacts with the MICOS-MIB complex and with the intracellular adaptor protein ankyrin B (ANKB), which connects the cytoskeleton to the plasma membrane; PERM1 contains a C-terminal transmembrane helix anchoring it to the outer mitochondrial membrane; Perm1 ablation in mice reduces muscle force, decreases mitochondrial membrane potential and Complex I activity, and reduces subsarcolemmal mitochondria (SSM) numbers. |
Protein interaction study (Co-IP/pulldown), complexome profiling, Perm1 knockout mice, mitochondrial membrane potential measurements, Complex I activity assay, SSM quantification, transmembrane helix identification |
Nature communications |
High |
34385433
|
| 2021 |
PERM1 associates with the outer mitochondrial membrane and is subject to proteasomal degradation regulated by phosphorylation of its PEST motif by casein kinase 2 (CK2); Perm1 ablation reduces lipin-1 protein expression, causes accumulation of specific phospholipid species, and leads to downregulation of mitochondrial transport proteins for amino acids and carnitines (SLC25A12/13/29/34, CPT2), with altered levels of lipid species, amino acids, and acylcarnitines in Perm1−/− mitochondria. |
Phosphoproteomics, identification of PEST motif phosphorylation by CK2, Perm1 knockout mice, isolation of Perm1-deficient mitochondria, proteomics, metabolomics, lipid analysis |
Journal of molecular and cellular cardiology |
High |
33549681
|
| 2021 |
Perm1 interacts with PGC-1α in cardiomyocytes and enhances activation of PGC-1 and ERR; Perm1 overexpression increases mitochondrial DNA copy number and oxidative capacity in neonatal mouse cardiomyocytes and reduces damage from hypoxia/reoxygenation stress. |
Co-immunoprecipitation, mitochondrial DNA copy number quantification, Seahorse oxidative capacity assay, hypoxia/reoxygenation cell death assay in neonatal mouse cardiomyocytes |
The Journal of biological chemistry |
Medium |
34029594
|
| 2022 |
PERM1 physically interacts with PPARα and PGC-1α; PERM1 localizes to proximal PPAR response elements (PPREs) in endogenous promoters of fatty acid oxidation genes (ChIP assay); PERM1 promotes transcription via PPREs in a PPARα- and PGC-1α-dependent manner; Perm1 knockout mice show downregulation of genes involved in fatty acid and carbohydrate metabolism in the heart. |
Systemic Perm1 KO mouse generation, RNA-seq and pathway analysis, ChIP assay at PPRE-containing promoters, co-immunoprecipitation (PERM1 with PPARα and PGC-1α), reporter gene assay |
Scientific reports |
High |
36028747
|
| 2022 |
PERM1 binds ERRα in cardiomyocytes and the mouse heart; PERM1 localizes to and activates ERR target promoters partly through ERRα; PERM1 functions as a transcriptional coactivator whose activity requires PGC-1α, BAG6, and KANK2 (identified as binding partners by mass spectrometry); Perm1−/− hearts show reduced ejection fraction, reduced phosphocreatine-to-ATP ratio, downregulation of oxidative phosphorylation proteins, and upregulation of glycolysis/polyol pathway. |
Perm1 KO mice, echocardiography, phosphocreatine-to-ATP ratio (31P-NMR or equivalent), proteomics, metabolomics, co-immunoprecipitation (PERM1-ERRα), mass spectrometry (binding partners: BAG6, KANK2), DNA binding assay, reporter gene assay, mammalian one-hybrid assay |
Frontiers in cardiovascular medicine |
High |
36419485
|
| 2024 |
PERM1 overexpression decreases total O-GlcNAcylated protein levels by decreasing OGT expression (via interaction with transcription repressor E2F1 to suppress Ogt promoter activity) and increasing OGA expression; excessive O-GlcNAcylation caused by loss of PERM1 increases O-GlcNAcylation of PGC-1α and causes dissociation of PGC-1α from PPARα; PERM1 overexpression restores mitochondrial respiration impaired by elevated O-GlcNAcylation. |
PERM1 overexpression in cardiomyocytes, luciferase reporter assay (Ogt promoter), co-immunoprecipitation (PERM1-E2F1; PGC-1α-PPARα), Oga siRNA knockdown, Seahorse mitochondrial respiration assay, Western blot for O-GlcNAcylation |
Journal of molecular and cellular cardiology |
High |
39581161
|
| 2024 |
AAV-mediated Perm1 gene delivery in mice enhances cardiac contractility and mitochondrial biogenesis; PERM1 physically interacts with troponin C (TnC) and AAV-Perm1 upregulates TnC protein levels, revealing a role for PERM1 in regulating cardiac contractility. |
AAV9-mediated Perm1 overexpression in mice, echocardiography, co-immunoprecipitation (PERM1-TnC), Western blot for TnC, mitochondrial DNA copy number |
American journal of physiology. Heart and circulatory physiology |
Medium |
39269449
|
| 2025 |
Perm1 activates the Nrf2 antioxidant pathway by promoting cysteine oxidation of Keap1, which reduces Keap1-Nrf2 interaction and inhibits Cul3-mediated ubiquitination/degradation of Nrf2; Cys121 and Cys746 in Perm1 are critical for Keap1 oxidation and cardioprotection against ischemia/reperfusion injury. |
Perm1 KO and overexpression in mouse myocardium, IR injury model, cysteine oxidation assay of Keap1, Co-immunoprecipitation (Keap1-Nrf2), Cul3-mediated degradation assay, site-directed mutagenesis of Perm1 Cys121 and Cys746, Nrf2 target gene expression |
JCI insight |
High |
42118582
|
| 2025 |
PERM1 is a direct downstream target of PRDM16; AAV9-Perm1 treatment of cardiac-specific Prdm16 KO mice improves contractile parameters, reduces LV dilation, and extends survival; Perm1 co-operates with PGC-1α downstream of PRDM16 to regulate fatty acid metabolism; co-immunoprecipitation shows PERM1 interacts with creatine kinase and troponin C. |
Transcriptomics and proteomics of cardiac-specific Prdm16 KO mice and iPSC-CMs, AAV9-Perm1 neonatal delivery, echocardiography, survival analysis, Co-immunoprecipitation (PERM1-creatine kinase; PERM1-TnC) |
bioRxivpreprint |
Medium |
42039588
|
| 2025 |
AAV9-PERM1 in a pressure-overload (TAC) mouse model preserves left ventricular ejection fraction, abrogates cardiac hypertrophy and fibrosis, preserves mitochondrial DNA copy number and TFAM levels, improves mitochondrial respiration, and suppresses TAC-induced O-GlcNAcylation; co-immunoprecipitation confirms PERM1 interactions with creatine kinase and troponin C. |
AAV9-PERM1 delivery before TAC surgery, echocardiography, mitochondrial DNA quantification, Seahorse mitochondrial respiration, histology (fibrosis/hypertrophy), Western blot (O-GlcNAcylation, TFAM), Co-immunoprecipitation |
bioRxivpreprint |
Medium |
41256646
|
| 2024 |
In human skeletal muscle, PERM1 protein localizes to the perinuclear region and is enriched in mitochondria (confirmed by immunolabeling, microscopy, and subcellular fractionation); HIIT training increases PERM1 isoform 2 protein and its target CKMT2. |
Immunolabeling, fluorescence microscopy, subcellular fractionation of human muscle biopsies, Western blotting |
Applied physiology, nutrition, and metabolism |
Medium |
41759080
|
| 2025 |
NOR-1 (NR4A3) drives PERM1 expression, and PERM1 in turn mediates NOR-1-dependent upregulation of myoglobin; NOR-1 overexpression in aged muscle increases PERM1, CKMT2, and myoglobin levels and enhances mitochondrial respiration. |
In vitro NOR-1 knockdown in C2C12 myotubes, NOR-1 overexpression in aged mouse muscle via electroporation/AAV, Western blotting, mitochondrial respiration assay, gene expression analysis |
FASEB journal |
Medium |
40235231
|