Affinage

UCP1

Mitochondrial brown fat uncoupling protein 1 · UniProt P25874

Length
307 aa
Mass
33.0 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UCP1 is the essential mediator of non-shivering thermogenesis in brown and beige adipocytes, dissipating the mitochondrial proton gradient as heat. It functions as a fatty acid anion/H⁺ symporter whose central cavity, open to the cytosolic side, accommodates both activating fatty acids and inhibitory purine nucleotides at overlapping binding sites; fatty acids induce a conformational change that relieves tonic nucleotide inhibition, and long-chain fatty acids remain tethered by hydrophobic interactions so that UCP1 effectively operates as an H⁺ uniporter (PMID:27984203, PMID:37336486, PMID:22952235). Acute thermogenic activation requires PKA-dependent phosphorylation and translocation of AIDA to the intermembrane space where it promotes UCP1 cysteine oxidation, mitochondrial ROS-driven sulfenylation of Cys253, formation of an MCU-EMRE-UCP1 thermoporter complex that couples calcium uptake to uncoupled respiration, and modulation by SIRT5-mediated desuccinylation and inner membrane phosphatidylethanolamine content (PMID:33664495, PMID:27027295, PMID:35977541, PMID:31000437, PMID:36827367). UCP1 operates in parallel with a UCP1-independent futile creatine cycle (CKB/TNAP) in brown adipose tissue, as demonstrated by synthetic lethality of UCP1 and CKB co-deletion for cold tolerance (PMID:38272036, PMID:40185737).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identifying the residues that control nucleotide binding and fatty acid cofactor function established the first molecular framework for how UCP1 switches between inhibited and active states.

    Evidence Site-directed mutagenesis with nucleotide binding assays, pH-dependence studies, and proton transport assays in vitro

    PMID:10454117

    Open questions at the time
    • No experimental structure to validate predicted helix architecture
    • Precise geometry of FA–nucleotide competition unknown
  2. 2001 High

    UCP1 knockout studies resolved the long-debated question of whether other UCPs contribute to adrenergic thermogenesis, demonstrating that UCP1 is absolutely required and cannot be substituted by UCP2 or UCP3.

    Evidence UCP1 KO mice with isolated mitochondria respiration, norepinephrine-challenge thermogenesis, and membrane potential measurements

    PMID:11239487 PMID:11709070

    Open questions at the time
    • UCP1-independent FA sensitivity of BAT mitochondria mechanistically unresolved
    • Compensatory remodeling in germline KO potentially confounds in vivo phenotype
  3. 2001 High

    Photoaffinity labeling and bioenergetic measurements localized the nucleotide-binding site to the cytosolic face and established fatty acids as self-regulating second messengers that both activate UCP1 and serve as oxidation substrates for recoupling.

    Evidence Photoaffinity labeling of native UCP1, proton conductance quantification in respiring isolated mitochondria

    PMID:11709069 PMID:11798029

    Open questions at the time
    • Gated-pore model lacked experimental structure
    • How FA oxidation rate controls UCP1 shut-off kinetics not quantified
  4. 2012 High

    Demonstrating that palmitate induces a conformational change in UCP1 resolved the paradox that fatty acids functionally overcome nucleotide inhibition without substantially altering nucleotide binding affinity.

    Evidence Fluorescence binding kinetics with MANT-GDP and limited proteolysis of UCP1 ± palmitate

    PMID:22952235

    Open questions at the time
    • Nature of conformational change unknown at atomic level
    • Whether all long-chain FAs produce identical conformational shift untested
  5. 2016 High

    Direct electrophysiology of UCP1 in mitoplasts established the FA anion/H⁺ symport mechanism and explained how long-chain FA hydrophobic tethering converts UCP1 into an effective H⁺ uniporter.

    Evidence Patch-clamp electrophysiology on inner mitochondrial membrane of brown fat mitoplasts

    PMID:27984203

    Open questions at the time
    • Structural basis of FA anion tethering not visualized
    • Whether short-chain FAs produce qualitatively different transport cycles in vivo
  6. 2016 High

    Identifying Cys253 sulfenylation as an ROS-dependent activation switch revealed a previously unknown redox-regulatory layer controlling UCP1 thermogenesis in vivo.

    Evidence Redox proteomics, C253 mutagenesis, mitochondrial ROS depletion, whole-body calorimetry in mice

    PMID:27027295

    Open questions at the time
    • Enzyme catalyzing sulfenylation not identified
    • How sulfenylation alters UCP1 channel gating structurally unknown
  7. 2019 High

    Discovery of SIRT5-dependent desuccinylation of specific UCP1 lysines established post-translational acylation as a modulator of UCP1 protein stability and activity.

    Evidence BAT-specific Sirt5 KO, mass spectrometry succinylation mapping, mutagenesis of modified lysines, respirometry

    PMID:31000437

    Open questions at the time
    • Whether succinylation is dynamically regulated during cold exposure unknown
    • How succinylation structurally destabilizes UCP1 not determined
  8. 2021 High

    The PKA-AIDA-UCP1 signaling axis was identified as the direct mechanistic link between sympathetic catecholamine input and UCP1 activation, with AIDA phosphorylation driving its translocation to the intermembrane space to promote UCP1 cysteine oxidation.

    Evidence Adipocyte-specific AIDA KO, S161A phospho-dead rescue, Co-IP of AIDA-UCP1, cold challenge phenotyping

    PMID:33664495

    Open questions at the time
    • How AIDA promotes cysteine oxidation mechanistically not defined
    • Whether AIDA acts on Cys253 specifically or additional cysteines unknown
  9. 2021 High

    C253A knock-in mice confirmed the physiological importance of Cys253 for thermogenesis and unexpectedly revealed sex-specific inflammatory pathology driven by adipose redox stress when this regulatory cysteine is absent.

    Evidence UCP1 C253A knock-in mouse with thermogenic and immune cell phenotyping

    PMID:34861155

    Open questions at the time
    • Mechanism of estrogen-mediated protection from C253A-driven inflammation not defined
    • Whether other UCP1 cysteines partially compensate for C253 loss
  10. 2022 High

    Discovery of the MCU-EMRE-UCP1 thermoporter complex established that mitochondrial calcium uptake is directly coupled to uncoupled respiration, providing a mechanism for coordinate acceleration of TCA cycle flux during thermogenesis.

    Evidence Reciprocal Co-IP, adipocyte-specific MCU/EMRE KO, EMRE-UCP1 fusion rescue, mitochondrial calcium flux measurements

    PMID:35977541

    Open questions at the time
    • Stoichiometry and structure of the MCU-EMRE-UCP1 complex unknown
    • Whether complex formation requires or is modulated by FA/nucleotide occupancy of UCP1
  11. 2023 High

    Cryo-EM structures of human UCP1 in three states provided the first atomic-resolution view, revealing cytosol-facing cavity architecture, overlapping DNP/ATP binding sites, and ATP-induced compaction that explains competitive inhibition.

    Evidence Cryo-EM structures of nucleotide-free, DNP-bound, and ATP-bound human UCP1

    PMID:37336486

    Open questions at the time
    • No FA-bound structure captured
    • Conformational dynamics during transport cycle not resolved
    • How Cys253 sulfenylation maps onto the structural states unknown
  12. 2023 High

    Molecular simulations and mutagenesis identified a hydrophobic triplet (F88/I187/W281) and E191 as determinants of purine nucleotide selectivity, explaining why pyrimidine nucleotides fail to inhibit UCP1.

    Evidence Molecular dynamics simulations with mutagenesis validated by yeast spheroplast respiration assays

    PMID:37147287

    Open questions at the time
    • Experimental structure of nucleotide-bound UCP1 at sufficient resolution to validate predicted orientations needed
    • Whether mutations alter FA binding cooperatively not assessed
  13. 2023 High

    Demonstrating that inner mitochondrial membrane PE content directly modulates UCP1 proton conductance revealed a lipid-environment dependency for thermogenic function.

    Evidence PSD KO mice, mitoplast patch-clamp of UCP1 proton currents, lipidomics, respirometry

    PMID:36827367

    Open questions at the time
    • Whether PE acts through direct protein-lipid contacts or membrane biophysical properties not distinguished
    • Other lipid species potentially modulating UCP1 not surveyed
  14. 2024 High

    Inducible double deletion of UCP1 and CKB resolved the confound of germline KO compensatory remodeling and established that UCP1 and the futile creatine cycle function as parallel, partially redundant thermogenic pathways in BAT.

    Evidence Inducible adipocyte-selective Cre deletion of Ucp1 and/or Ckb, cold tolerance testing, regeneration analysis

    PMID:38272036 PMID:40185737

    Open questions at the time
    • Quantitative contribution of each pathway at different temperatures not defined
    • Whether additional UCP1-independent mechanisms beyond FCC exist in classical BAT

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of fatty acid-induced conformational activation (no FA-bound structure exists), the mechanism by which AIDA promotes UCP1 cysteine oxidation, the stoichiometry and regulation of the MCU-EMRE-UCP1 complex, and the full post-translational modification landscape governing UCP1 activity in vivo.
  • No FA-bound cryo-EM structure
  • AIDA mechanism of action on UCP1 cysteine oxidation undefined
  • MCU-EMRE-UCP1 complex stoichiometry and structural basis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008289 lipid binding 3
Localization
GO:0005739 mitochondrion 6
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-1430728 Metabolism 3 GO:0005215 transporter activity 2 R-HSA-162582 Signal Transduction 2
Partners
AIDACIDEAEMREGATA3MCUMICU1PGC1ASIRT5
Complex memberships
MCU-EMRE-UCP1 thermoporter complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Cryo-EM structures of human UCP1 in nucleotide-free, DNP-bound, and ATP-bound states reveal that the central cavity is open to the cytosolic side; DNP binds inside the cavity contacting TM2 and TM6, while ATP binds the same cavity and induces inward bending of TM1, TM4, TM5, and TM6, resulting in a more compact structure; ATP and DNP binding sites overlap, explaining competitive inhibition of proton-conducting activity by ATP. Cryo-EM structure determination of human UCP1 in three states, combined with functional analysis Nature High 37336486
2016 UCP1 Cys253 is sulfenylated during thermogenesis in brown adipose tissue; mutation of Cys253 desensitizes UCP1 to adrenergic activation and uncoupling, and pharmacological depletion of mitochondrial ROS causes hypothermia and inhibits UCP1-dependent energy expenditure, establishing mitochondrial ROS as an upstream activator of UCP1 through cysteine sulfenylation. In vivo ROS depletion, site-directed mutagenesis of UCP1 Cys253, redox proteomics of brown adipose tissue, whole-body energy expenditure measurements Nature High 27027295
2021 UCP1 Cys253-null (C253A) mice show significantly compromised thermogenic responses but no measurable effect on fat accumulation; loss of C253 causes adipose tissue redox stress, driving immune cell infiltration and systemic inflammatory pathology in males but not females, with elevated systemic estrogen reversing the male-specific pathology. Generation of UCP1 C253A knock-in mouse, thermogenic phenotyping, adipose tissue redox and immune cell analyses Cell metabolism High 34861155
2016 UCP1 transports fatty acid anions as substrates and operates as an unusual FA anion/H+ symporter; long-chain FA anions cannot easily dissociate from UCP1 due to hydrophobic interactions, so a single long-chain FA participates in many H+ transport cycles, making UCP1 effectively an H+ uniport in the presence of long-chain FA; long-chain FA also competitively remove tonic inhibition by cytosolic purine nucleotides. Patch-clamp electrophysiology applied directly to the inner mitochondrial membrane of brown fat mitoplasts Biochimie High 27984203
2022 Common protonophoric uncouplers (DNP, FCCP) induce H+ leak through UCP1 and AAC in a protein-dependent manner; molecular docking using AAC structures shows protonophore and long-chain fatty acid binding sites overlap with the putative ADP/ATP-binding site; a mathematical model proposes mechanism of uncoupler-dependent H+ leak through AAC and UCP1. Direct electrophysiological measurement of mitochondrial H+ currents, molecular docking using AAC structures, mathematical modeling, genetic loss-of-function (UCP1/AAC KO) Nature High 35614225
1999 Structure-function analysis of UCP1 by mutagenesis identified: fatty acids act as cofactor providing H+-shuttling carboxyl groups in the translocation channel; two pH sensors (E190 and H214) control nucleotide binding; three conserved intrahelical arginines are essential for nucleotide binding; fatty acids and nucleotides compete to regulate UCP1 activity. Site-directed mutagenesis, nucleotide binding assays, pH-dependence studies, proton transport assays International journal of obesity and related metabolic disorders High 10454117
2012 Fatty acids induce a conformational change in UCP1: palmitate dramatically alters binding kinetics of a fluorescent GDP analog and accelerates enzymatic proteolysis of UCP1, reconciling the apparent discrepancy that fatty acids competitively overcome nucleotide inhibition functionally but have little effect on nucleotide binding affinity. Fluorescence binding kinetics with MANT-GDP analog, limited proteolysis assay of UCP1 in presence/absence of palmitate The Journal of biological chemistry High 22952235
2001 UCP1 ablation experiments establish that adaptive adrenergic non-shivering thermogenesis is fully dependent on UCP1; norepinephrine-induced thermogenesis in brown-fat cells is absolutely UCP1-dependent; isolated brown-fat mitochondria from UCP1-ablated mice are fully coupled; UCP2/UCP3 cannot functionally substitute for UCP1 in thermogenesis despite high expression in UCP1-KO brown fat. UCP1 knockout mouse analysis, isolated brown-fat mitochondria respiration assays, norepinephrine-challenge thermogenesis measurements Biochimica et biophysica acta High 11239487
2001 UCP1 ablated brown-fat mitochondria are fully coupled (no need for GDP addition) but retain a UCP1-independent 50-fold higher sensitivity to free fatty acids de-energization compared to liver mitochondria; this UCP1-independent fatty acid sensitivity is of a different nature than UCP1-mediated uncoupling. Isolated mitochondria respiration and membrane potential measurements from UCP1-KO and WT brown fat vs. liver Biochemical Society transactions High 11709070
2019 Sirt5-mediated desuccinylation regulates UCP1; Sirt5 KO in BAT increases global succinylation including succinylation of UCP1 at two specific lysines; mutation of these lysines to acyl-mimetic glutamine/glutamic acid significantly decreases UCP1 stability and activity; reduced UCP1 function in Sirt5KO BAT results in impaired mitochondrial respiration. BAT-specific Sirt5 knockout, mass spectrometry-based succinylation quantification, site-directed mutagenesis of UCP1 succinylated lysines, high-resolution respirometry Molecular cell High 31000437
2021 UCP1 governs succinate clearance from circulation: without UCP1, brown and beige fat exhibit diminished capacity to clear succinate; UCP1-KO mice have elevated extracellular succinate in liver tissue that drives inflammation through SUCNR1 in stellate cells and macrophages; increasing brown/beige adipocyte content antagonizes SUCNR1-dependent inflammatory signaling in liver. UCP1-KO mouse metabolomics, succinate supplementation/clearance assays, SUCNR1 receptor ligation studies, liver immune cell infiltration analysis Nature metabolism High 34002097
2022 Mitochondrial calcium uniporter (MCU) recruits UCP1 through EMRE to form an MCU-EMRE-UCP1 thermoporter complex upon adrenergic stimulation; complex formation increases mitochondrial calcium uptake to accelerate the TCA cycle and supply more protons for uncoupled respiration; MICU1 negatively regulates thermogenesis by inhibiting complex formation; deletion of Mcu or Emre in brown adipocytes impairs thermogenesis. Co-immunoprecipitation, adipocyte-specific MCU/EMRE knockout mice, thermogenic phenotyping, mitochondrial calcium flux measurements, EMRE-UCP1 fusion protein rescue experiments Cell metabolism High 35977541
2021 AIDA, located in the outer mitochondrial membrane, is phosphorylated at S161 by PKA upon catecholamine signaling; phosphorylated AIDA translocates to the intermembrane space where it binds and activates UCP1 by promoting cysteine oxidation; adipocyte-specific AIDA depletion abrogates UCP1-dependent thermogenesis causing hypothermia; S161A-AIDA fails to restore the cold response, establishing the PKA-AIDA-UCP1 axis as a direct mechanistic link between sympathetic input and thermogenesis. PKA phosphorylation assay, subcellular fractionation, Co-IP of AIDA-UCP1, adipocyte-specific AIDA knockout, rescue with WT vs. S161A-AIDA, cold exposure phenotyping, sympathetic denervation Nature cell biology High 33664495
2023 Phosphatidylethanolamine (PE) in the inner mitochondrial membrane modulates UCP1-dependent proton conductance; deletion of phosphatidylserine decarboxylase (PSD) reduces mitochondrial PE, causes cold intolerance, and specifically lowers UCP1-dependent respiration without compromising electron transfer or ATP synthesis; direct UCP1 proton current measured in PE-deficient mitoplasts is reduced. Mitochondrial lipidomics, PSD knockout mice, high-resolution respirometry, patch-clamp of UCP1 proton currents in mitoplasts, β3-AR agonist challenge Science advances High 36827367
2023 Molecular simulations predict GDP and GTP bind UCP1 at the common substrate binding site in an upright orientation with base moiety interacting with R92 and E191; a hydrophobic triplet F88/I187/W281 forms contacts with nucleotides; I187A and W281A mutations increase fatty acid-induced uncoupling and partially suppress nucleotide inhibition; the F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high nucleotide concentrations; E191 and W281 interact with purine but not pyrimidine bases, explaining selective inhibition by purine nucleotides. Molecular dynamics simulations, site-directed mutagenesis, yeast spheroplast respiration assays Nature communications High 37147287
2001 The nucleotide-binding site of UCP1 was identified on the outer face of the inner membrane by photoaffinity labeling as a 32 kDa protein; fatty acids liberated by β3-adrenergic receptor activation act as both self-regulating second messengers for UCP1 activation and substrates for oxidation; fatty acid concentration increases lower protonmotive force below respiratory control threshold, initiating rapid thermogenesis; oxidation of residual fatty acid recouples mitochondria upon cessation of receptor activation. Photoaffinity labeling, isolated brown adipocyte respiration measurements, proton conductance quantification in respiring mitochondria Biochemical Society transactions High 11709069
2001 UCP1 is proposed to function as a gated pore; the transmembrane α-helices form a hydrophilic translocation channel and matrix loops form gating domains; the nucleotide enters from the cytosolic side and binds deep inside the protein; three arginine residues on helices II, IV, and VI interact with phosphate groups; His214 and Glu190 regulate pH-dependent nucleotide access to the binding center. Photoaffinity labeling, mutagenesis of charged residues, nucleotide binding assays, structural modeling IUBMB life Medium 11798029
2017 Adipose triglyceride lipase (ATGL) activity is required for UCP1 activation in intact brown and brite adipocytes; siRNA knockdown of ATGL blocks UCP1-dependent respiration measured by respirometry comparing WT and UCP1-KO cells. siRNA knockdown of ATGL, respirometry comparing WT vs. UCP1-KO adipocytes, GDP-based quantification of UCP1-specific respiration Biochimie Medium 27986537
2017 UCP3 in BAT is differently regulated than UCP1: unlike UCP1, UCP3 can be fully inhibited by all purine nucleotides and IC50 increases with decreased PN phosphorylation; fatty acids compete with all PNs bound to UCP1 but only with ATP bound to UCP3; phosphate is identified as a novel inhibitor of both UCP3 and UCP1 acting independently of purine nucleotides; conserved arginines in the PN-binding pocket contribute differently to inhibition of UCP1 vs. UCP3. Atomic force microscopy, electrophysiology of recombinant proteins reconstituted in planar bilayer membranes, mutagenesis of conserved arginines Biochimica et biophysica acta. Biomembranes Medium 29212043
2019 CIDEA shuttles from lipid droplets to the nucleus via a bipartite nuclear localization signal in a concentration-dependent manner during adipocyte browning; in the nucleus CIDEA inhibits LXRα repression of the UCP1 enhancer and strengthens PPARγ binding to the UCP1 enhancer, thereby driving UCP1 transcription; CRISPR-Cas9 knockout of CIDEA suppresses UCP1 expression and browning in primary human adipocytes. Modified dual-RNA CRISPR-Cas9nD10A knockout, luciferase reporter assays with UCP1 enhancer, nuclear fractionation, ChIP for PPARγ and LXRα on UCP1 enhancer iScience Medium 31563853
2010 T3 increases the adrenergic stimulation of UCP1 expression primarily via the TRβ1 isoform in rat brown adipocytes; T3 inhibits D2 enzyme activity post-transcriptionally through proteasomal degradation, shortening D2 half-life; TRα1 agonist CO23 had minimal effect on UCP1, confirming TRβ1 specificity. Cultured rat brown adipocytes treated with selective TRβ1 (GC-1) and TRα1 (CO23) agonists, D2 activity assays, D2 stability measurement, UCP1 mRNA quantification Endocrinology Medium 20719854
2015 Post-transcriptional regulation of Ucp1 mRNA is mediated by the Cnot7-Tob-BRF1 axis; Tob interacts with BRF1 which binds an AU-rich element in the Ucp1 3'-UTR; Cnot7/Tob double-KO mice show elevated Ucp1 mRNA with elongated poly(A) tails in iWAT and are resistant to diet-induced obesity; Tob mutant unable to bind Cnot7 stabilizes Ucp1 3'-UTR-containing mRNA. Cnot7 and Tob KO mice, poly(A) tail length analysis, mRNA stability assays with mutant Tob, BRF1 knockdown, AU-rich element mapping Cell reports Medium 26711342
2010 KLF11 directly binds the UCP1 promoter via GC-boxes and is essential for UCP1 expression during brown adipocyte differentiation; KLF15 binds UCP1 promoter via GT-boxes and co-transfection of both KLF11 and KLF15 enhances UCP1 expression level during differentiation. Chromatin immunoprecipitation (ChIP), co-transfection in mesenchymal stem cell line, luciferase reporter assays Biochemical and biophysical research communications Medium 20709022
2024 Inducible adipocyte-selective deletion of UCP1 alone does not cause cold-induced hypothermia in most mice (unlike germline KO), but co-deletion of UCP1 and creatine kinase b (CKB) exacerbates cold intolerance, establishing that UCP1 and CKB function in parallel thermogenic pathways; following deletion, moderate cold triggers regeneration of brown adipocytes that coordinately restore both UCP1 and CKB expression. Inducible adipocyte-selective Cre-mediated deletion of Ucp1 and/or Ckb, cold tolerance testing, adipocyte regeneration analysis Cell metabolism High 38272036
2025 The Futile Creatine Cycle (FCC), involving CKB-mediated creatine phosphorylation and TNAP-mediated phosphocreatine hydrolysis in mitochondria, operates as a UCP1-independent thermogenic mechanism in classical BAT; reintroducing mitochondrial-targeted CKB into interscapular brown adipocytes of UCP1/CKB double-KO mice restores thermogenesis and cold tolerance in a TNAP-dependent manner; inducible adipocyte-specific co-deletion of TNAP and UCP1 causes severe cold intolerance. In vivo reintroduction of mitochondria-targeted CKB in UCP1/CKB double-KO adipocytes, inducible adipocyte-specific TNAP+UCP1 double KO, cold tolerance testing Nature communications High 40185737
2015 UCP1 is expressed in neurons of thirteen-lined ground squirrels and expression increases during hibernation; squirrel UCP1 functions as a typical thermogenic protein in vitro; mitochondria from torpid squirrel brain show high levels of palmitate-induced uncoupling; torpid squirrel brain temperature is maintained significantly elevated above ambient and above brown adipose tissue temperature, suggesting UCP1-mediated local neuronal thermogenesis. Differential transcriptomics, immunohistochemistry, mitochondrial uncoupling assays in vitro, brain temperature telemetry Proceedings of the National Academy of Sciences of the United States of America Medium 25605929
2020 GATA3 directly binds the UCP1 promoter region and interacts with PGC-1α via co-immunoprecipitation to increase UCP1 transcription; GATA3 expression is elevated in cold-exposed inguinal adipose tissue; lentiviral GATA3 overexpression in vivo increases thermogenic gene expression including UCP1. Luciferase reporter assays with UCP1 promoter, co-immunoprecipitation of GATA3 and PGC-1α, ChIP, lentiviral overexpression/knockdown in vitro and in vivo Metabolism: clinical and experimental Medium 32473155
2004 UCP1 protein is detected in mitochondria from rat thymocytes by immunoblot analysis using a UCP1-specific antibody, identifying UCP1 expression outside of brown adipose tissue. Subcellular fractionation and immunoblot analysis of thymocyte mitochondria Biochemical Society transactions Low 15506965
2017 Inflammation downregulates UCP1 expression in brown adipocytes via DBC1-mediated inhibition of SIRT1; IL1β increases DBC1 expression and reduces dbcAMP-induced Ucp1 induction; silencing SIRT1 attenuates Ucp1 induction; resveratrol (SIRT1 activator) partially rescues Ucp1 downregulation by inflammation both in vitro and in LPS-infused mice. SIRT1 siRNA knockdown, DBC1 expression analysis, resveratrol treatment, dbcAMP stimulation of immortalized brown adipocytes, in vivo LPS infusion International journal of molecular sciences Medium 28481291

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. The Biochemical journal 640 10620491
2018 New Advances in Adaptive Thermogenesis: UCP1 and Beyond. Cell metabolism 604 30503034
2017 UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nature medicine 520 29131158
2001 UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochimica et biophysica acta 490 11239487
2016 Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature 377 27027295
1998 Role of UCP homologues in skeletal muscles and brown adipose tissue: mediators of thermogenesis or regulators of lipids as fuel substrate? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 279 9619450
2020 UCP1 Dependent and Independent Thermogenesis in Brown and Beige Adipocytes. Frontiers in endocrinology 205 32849287
2019 Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation. Molecular cell 162 31000437
2008 UCP1: its involvement and utility in obesity. International journal of obesity (2005) 157 19136989
2021 UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nature metabolism 145 34002097
2011 Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. American journal of physiology. Cell physiology 145 22075692
2010 Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice. American journal of physiology. Regulatory, integrative and comparative physiology 137 20826705
2020 UCP1-independent thermogenesis. The Biochemical journal 126 32059055
2017 Long-Term Cold Adaptation Does Not Require FGF21 or UCP1. Cell metabolism 109 28768181
2022 Mitochondrial uncouplers induce proton leak by activating AAC and UCP1. Nature 101 35614225
2002 Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cellular and molecular life sciences : CMLS 100 12475182
2014 Brite/beige fat and UCP1 - is it thermogenesis? Biochimica et biophysica acta 96 24530356
2016 UCP1, the mitochondrial uncoupling protein of brown adipocyte: A personal contribution and a historical perspective. Biochimie 95 27916641
2012 The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus. Arquivos brasileiros de endocrinologia e metabologia 94 22790465
2005 SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on UCP activity. The EMBO journal 93 16281056
2020 FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis. Nature communications 89 32184391
2017 Low protein-induced increases in FGF21 drive UCP1-dependent metabolic but not thermoregulatory endpoints. Scientific reports 88 28811495
2009 The polymorphisms of UCP1 genes associated with fat metabolism, obesity and diabetes. Molecular biology reports 82 19444646
2001 A history of UCP1. Biochemical Society transactions 81 11709069
2016 UCP1: A transporter for H+ and fatty acid anions. Biochimie 80 27984203
2020 UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice. Metabolism: clinical and experimental 78 33065161
2019 CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells. iScience 77 31563853
2013 FTO deficiency induces UCP-1 expression and mitochondrial uncoupling in adipocytes. Endocrinology 77 23751871
2019 Melatonin/PGC1A/UCP1 promotes tumor slimming and represses tumor progression by initiating autophagy and lipid browning. Journal of pineal research 75 31469445
2018 Mechanisms underlying UCP1 dependent and independent adipocyte thermogenesis. Obesity reviews : an official journal of the International Association for the Study of Obesity 72 30450758
2010 Prodigiosin production by Serratia marcescens UCP 1549 using renewable-resources as a low cost substrate. Molecules (Basel, Switzerland) 70 20938403
2024 Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB. Cell metabolism 64 38272036
1999 Structure-function relationship in UCP1. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 64 10454117
2022 The mitochondrial calcium uniporter engages UCP1 to form a thermoporter that promotes thermogenesis. Cell metabolism 63 35977541
2017 Quantification of UCP1 function in human brown adipose tissue. Adipocyte 62 28453364
2010 The T3 receptor beta1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. Endocrinology 61 20719854
2023 Structural basis for the binding of DNP and purine nucleotides onto UCP1. Nature 56 37336486
2019 Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 56 31131187
2015 The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue. Biochimica et biophysica acta 55 26518386
2012 Fatty acids change the conformation of uncoupling protein 1 (UCP1). The Journal of biological chemistry 54 22952235
2015 Post-transcriptional Stabilization of Ucp1 mRNA Protects Mice from Diet-Induced Obesity. Cell reports 51 26711342
2021 Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation. Cell metabolism 50 34861155
2018 Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1). Biochimica et biophysica acta. Bioenergetics 50 30414927
2017 A nutritional perspective on UCP1-dependent thermogenesis. Biochimie 50 28057582
2017 Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells. Scientific reports 50 28117414
2001 Life without UCP1: mitochondrial, cellular and organismal characteristics of the UCP1-ablated mice. Biochemical Society transactions 50 11709070
2019 At thermoneutrality, acute thyroxine-induced thermogenesis and pyrexia are independent of UCP1. Molecular metabolism 49 31151797
2017 Inflammation Downregulates UCP1 Expression in Brown Adipocytes Potentially via SIRT1 and DBC1 Interaction. International journal of molecular sciences 49 28481291
2011 Evaluation antimicrobial and antiadhesive properties of the biosurfactant Lunasan produced by Candida sphaerica UCP 0995. Current microbiology 48 21327556
2023 Mitochondrial phosphatidylethanolamine modulates UCP1 to promote brown adipose thermogenesis. Science advances 47 36827367
2019 Glucocorticoid-Induced Obesity Develops Independently of UCP1. Cell reports 47 31067456
2008 An ancient look at UCP1. Biochimica et biophysica acta 47 18396149
1999 Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially. Biochimica et biophysica acta 45 9989288
2015 Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation. Proceedings of the National Academy of Sciences of the United States of America 44 25605929
2006 Regulation of UCP1 and UCP3 in arctic ground squirrels and relation with mitochondrial proton leak. Journal of applied physiology (Bethesda, Md. : 1985) 43 16782837
2017 Thermoneutrality but Not UCP1 Deficiency Suppresses Monocyte Mobilization Into Blood. Circulation research 42 28696252
2024 Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes. Cell metabolism 41 39084216
2017 What Ignites UCP1? Cell metabolism 41 29117542
2010 Transcriptional regulation of a brown adipocyte-specific gene, UCP1, by KLF11 and KLF15. Biochemical and biophysical research communications 40 20709022
2018 A dual Ucp1 reporter mouse model for imaging and quantitation of brown and brite fat recruitment. Molecular metabolism 39 30580967
2001 The mitochondrial uncoupling protein UCP1: a gated pore. IUBMB life 39 11798029
2019 UCP1 expression-associated gene signatures of human epicardial adipose tissue. JCI insight 38 30996144
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