UCP2 (SLC25A8) is a member of the mitochondrial carrier (SLC25) family located in the inner mitochondrial membrane. Although named for its homology to the thermogenic uncoupling protein UCP1, reconstitution and silencing studies show that its principal activity is an antiport that exports four-carbon Krebs-cycle intermediates (malate, oxaloacetate, aspartate) from the matrix in exchange for phosphate plus a proton. By draining C4 metabolites it limits the oxidation of acetyl-CoA-producing substrates such as glucose, favours glutaminolysis, and lowers the ATP/ADP ratio and mitochondrial ROS production. Reconstituted UCP2 also conducts protons when activated by long-chain fatty acids (inhibited by purine nucleotides) and transports chloride, but the physiological weight of this mild uncoupling is debated, and it does not mediate adaptive thermogenesis. UCP2 is widely expressed (adipose tissue, muscle, macrophages, pancreatic islets, hypothalamus). In pancreatic beta cells it restrains glucose-stimulated insulin secretion, and heterozygous impaired-function variants have been reported in congenital hyperinsulinism, an association that remains disputed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000266 mitochondrial fission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial fission (mouse VMH neurons). Reason: UCP2 is required for glucose-induced DRP1-dependent fission in mouse hypothalamic neurons; a context-specific role, not core. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). |
| GO:0000266 mitochondrial fission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial fission (mouse VMH neurons). Reason: UCP2 is required for glucose-induced DRP1-dependent fission in mouse hypothalamic neurons; a context-specific role, not core. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). |
| GO:0000303 response to superoxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to superoxide (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0001666 response to hypoxia | IDA PMID:22292025 UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic c... | KEEP AS NON CORE | Summary: Response to hypoxia (IDA, A549 overexpression). Reason: Overexpressed UCP2 limits ROS accumulation and apoptosis in hypoxic A549 cells; a protective, downstream effect of its mitochondrial transport function. Supporting Evidence: PMID:22292025 Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS) accumulation (P<0.001) and apoptosis (P<0.001) compared to the controls when the cells were exposed to hypoxia. |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to hypoxia (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Long-chain fatty acid transmembrane transporter activity (ISS from mouse). Reason: The proposed mechanism of UCP-mediated proton leak is fatty-acid anion flipping across the inner membrane; supported for the mouse orthologue but secondary to the C4-dicarboxylate carrier activity. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt proton entry into the mitochondrial matrix affecting ATP turnover as a protection mechanism against oxidative stress. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI). Reason: Uninformative. The KRTAP10-7 interaction is a binary interactome screen hit and the MICU1 association is better described by the calcium-uptake process term; removing protein binding does not imply the interactions are false. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005515 protein binding | IPI PMID:27642082 PRMT1-mediated methylation of MICU1 determines the UCP2/3 de... | REMOVE | Summary: Protein binding (IPI). Reason: Uninformative. The KRTAP10-7 interaction is a binary interactome screen hit and the MICU1 association is better described by the calcium-uptake process term; removing protein binding does not imply the interactions are false. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MODIFY | Summary: Mitochondrion. Reason: Correct but less specific than the established inner-membrane location; UCP2 is an inner-membrane mitochondrial carrier, and the gene already carries GO:0005743 on seven rows. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MODIFY | Summary: Mitochondrion. Reason: Correct but less specific than the established inner-membrane location; UCP2 is an inner-membrane mitochondrial carrier, and the gene already carries GO:0005743 on seven rows. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; |
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | NAS PMID:9196039 UCP3: an uncoupling protein homologue expressed preferential... | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-166214 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-166220 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-166387 | ACCEPT | Summary: Mitochondrial inner membrane. Reason: UCP2 is a multi-pass SLC25 carrier of the inner mitochondrial membrane, where it exchanges C4 metabolites for phosphate. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0006096 glycolysis | IMP PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | MARK AS OVER ANNOTATED | Summary: Glycolysis (IMP, UCP2 silencing in HepG2 cells). Reason: Silencing UCP2 changed glucose oxidation and lactate release, showing that UCP2 influences the balance between glycolysis and mitochondrial oxidation by exporting C4 metabolites. UCP2 does not perform a glycolytic step; the effect is regulatory/indirect. Supporting Evidence: PMID:24395786 by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. |
| GO:0006541 L-glutamine metabolic process | IMP PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | MARK AS OVER ANNOTATED | Summary: L-glutamine metabolic process (IMP, HepG2 silencing). Reason: UCP2 export of C4 metabolites enhances glutaminolysis, but UCP2 does not catalyse glutamine metabolism; indirect involvement. Supporting Evidence: PMID:24395786 by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. |
| GO:0006839 mitochondrial transport | IEA GO_REF:0000107 | TOO GENERAL | Summary: Mitochondrial transport. Reason: True of UCP2 but uninformative, because GO:1990542 mitochondrial transmembrane transport, accepted in this review on IBA and IMP rows, already entails it. GO:1990542 is a confirmed descendant of GO:0006839. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0008271 secondary active sulfate transmembrane transporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | KEEP AS NON CORE | Summary: Secondary active sulfate transmembrane transporter activity (IDA, reconstitution). Reason: Reconstituted UCP2 exchanges sulfate for phosphate in vitro (Rhea:73391); a substrate-range property of the carrier, not its physiological role. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. |
| GO:0009409 response to cold | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Response to cold (IBA). Reason: Inherited from the UCP1-containing clade; UCP2 does not mediate adaptive thermogenesis. Cold-responsiveness is a UCP1 property not supported for UCP2. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001183920 SUPPORTS SOURCE BUT NOT TARGET Node grounded only in Ucp1 cold-response data; UCP2 diverged and does not mediate thermogenesis. MGI:MGI:98894 SUPPORTS SOURCE BUT NOT TARGET Thermogenic UCP1 orthologue providing the experimental grounding of the node. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt adaptive thermogenesis (By similarity) |
| GO:0009749 response to glucose | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to glucose (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0015078 proton transmembrane transporter activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Proton transmembrane transporter activity. Reason: Reconstituted UCP2 conducts protons when activated by long-chain fatty acids and inhibited by purine nucleotides, so the capability is directly measured and the term is kept. It is non-core because the core activity is the C4-dicarboxylate/phosphate antiport, and because a measured conductance is not evidence of the flux mattering in vivo. That is also what separates this row from GO:0017077 oxidative phosphorylation uncoupler activity, which is marked over-annotated: this term names a transport capability, whereas that one names a physiological consequence - the proton leak being large enough to uncouple respiration from ATP synthesis - which the same evidence does not support, and which UniProt denies for thermogenesis. Keeping one and rejecting the other is therefore not inconsistent; the two terms make claims of different strength. Supporting Evidence: PMID:26182433 transported protons in the presence of physiologically-relevant fatty acid (FA) activators. PMID:22524567 All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0015078 proton transmembrane transporter activity | IDA PMID:22524567 Toward understanding the mechanism of ion transport activity... | KEEP AS NON CORE | Summary: Proton transmembrane transporter activity. Reason: Reconstituted UCP2 conducts protons when activated by long-chain fatty acids and inhibited by purine nucleotides, so the capability is directly measured and the term is kept. It is non-core because the core activity is the C4-dicarboxylate/phosphate antiport, and because a measured conductance is not evidence of the flux mattering in vivo. That is also what separates this row from GO:0017077 oxidative phosphorylation uncoupler activity, which is marked over-annotated: this term names a transport capability, whereas that one names a physiological consequence - the proton leak being large enough to uncouple respiration from ATP synthesis - which the same evidence does not support, and which UniProt denies for thermogenesis. Keeping one and rejecting the other is therefore not inconsistent; the two terms make claims of different strength. Supporting Evidence: PMID:26182433 transported protons in the presence of physiologically-relevant fatty acid (FA) activators. PMID:22524567 All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0015078 proton transmembrane transporter activity | IDA PMID:26182433 A biophysical study on molecular physiology of the uncouplin... | KEEP AS NON CORE | Summary: Proton transmembrane transporter activity. Reason: Reconstituted UCP2 conducts protons when activated by long-chain fatty acids and inhibited by purine nucleotides, so the capability is directly measured and the term is kept. It is non-core because the core activity is the C4-dicarboxylate/phosphate antiport, and because a measured conductance is not evidence of the flux mattering in vivo. That is also what separates this row from GO:0017077 oxidative phosphorylation uncoupler activity, which is marked over-annotated: this term names a transport capability, whereas that one names a physiological consequence - the proton leak being large enough to uncouple respiration from ATP synthesis - which the same evidence does not support, and which UniProt denies for thermogenesis. Keeping one and rejecting the other is therefore not inconsistent; the two terms make claims of different strength. Supporting Evidence: PMID:26182433 transported protons in the presence of physiologically-relevant fatty acid (FA) activators. PMID:22524567 All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0015078 proton transmembrane transporter activity | IDA PMID:33373220 Functional Oligomeric Forms of Uncoupling Protein 2: Strong ... | KEEP AS NON CORE | Summary: Proton transmembrane transporter activity. Reason: Reconstituted UCP2 conducts protons when activated by long-chain fatty acids and inhibited by purine nucleotides, so the capability is directly measured and the term is kept. It is non-core because the core activity is the C4-dicarboxylate/phosphate antiport, and because a measured conductance is not evidence of the flux mattering in vivo. That is also what separates this row from GO:0017077 oxidative phosphorylation uncoupler activity, which is marked over-annotated: this term names a transport capability, whereas that one names a physiological consequence - the proton leak being large enough to uncouple respiration from ATP synthesis - which the same evidence does not support, and which UniProt denies for thermogenesis. Keeping one and rejecting the other is therefore not inconsistent; the two terms make claims of different strength. Supporting Evidence: PMID:26182433 transported protons in the presence of physiologically-relevant fatty acid (FA) activators. PMID:22524567 All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0015078 proton transmembrane transporter activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Proton transmembrane transporter activity. Reason: Reconstituted UCP2 conducts protons when activated by long-chain fatty acids and inhibited by purine nucleotides, so the capability is directly measured and the term is kept. It is non-core because the core activity is the C4-dicarboxylate/phosphate antiport, and because a measured conductance is not evidence of the flux mattering in vivo. That is also what separates this row from GO:0017077 oxidative phosphorylation uncoupler activity, which is marked over-annotated: this term names a transport capability, whereas that one names a physiological consequence - the proton leak being large enough to uncouple respiration from ATP synthesis - which the same evidence does not support, and which UniProt denies for thermogenesis. Keeping one and rejecting the other is therefore not inconsistent; the two terms make claims of different strength. Supporting Evidence: PMID:26182433 transported protons in the presence of physiologically-relevant fatty acid (FA) activators. PMID:22524567 All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0015108 chloride transmembrane transporter activity | IDA PMID:22524567 Toward understanding the mechanism of ion transport activity... | KEEP AS NON CORE | Summary: Chloride transmembrane transporter activity (IDA, reconstitution). Reason: Reconstituted UCP2 transports chloride; physiological relevance unclear. Supporting Evidence: PMID:22524567 Neuronal UCPs also exhibit transmembrane chloride transport activity. PMID:26182433 exhibited chloride transport activities that were partially inhibited by FAs. |
| GO:0015108 chloride transmembrane transporter activity | IDA PMID:26182433 A biophysical study on molecular physiology of the uncouplin... | KEEP AS NON CORE | Summary: Chloride transmembrane transporter activity (IDA, reconstitution). Reason: Reconstituted UCP2 transports chloride; physiological relevance unclear. Supporting Evidence: PMID:22524567 Neuronal UCPs also exhibit transmembrane chloride transport activity. PMID:26182433 exhibited chloride transport activities that were partially inhibited by FAs. |
| GO:0015131 oxaloacetate transmembrane transporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | ACCEPT | Summary: Oxaloacetate transmembrane transporter activity (IDA). Reason: Core substrate: reconstituted UCP2 exchanges oxaloacetate for phosphate plus a proton. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0015140 malate transmembrane transporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | ACCEPT | Summary: Malate transmembrane transporter activity (IDA). Reason: Core substrate of the UCP2 C4-dicarboxylate carrier. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. file:human/UCP2/UCP2-uniprot.txt anions including L-malate, L-aspartate, phosphate and chloride ions (PubMed:22524567, PubMed:24395786, PubMed:26182433). |
| GO:0015183 L-aspartate transmembrane transporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | ACCEPT | Summary: L-aspartate transmembrane transporter activity (IDA). Reason: Aspartate is exchanged for phosphate by reconstituted UCP2. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. file:human/UCP2/UCP2-uniprot.txt anions including L-malate, L-aspartate, phosphate and chloride ions (PubMed:22524567, PubMed:24395786, PubMed:26182433). |
| GO:0015297 antiporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | MODIFY | Summary: Antiporter activity (IDA). Reason: Correct but general: UCP2 exchanges C4 dicarboxylates (malate, oxaloacetate, aspartate, malonate) for phosphate plus a proton, which is exactly dicarboxylate:phosphate antiporter activity. Proposed replacements: dicarboxylate:phosphate antiporter activity Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0015740 C4-dicarboxylate transport | IMP PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | ACCEPT | Summary: C4-dicarboxylate transport (IMP). Reason: Core process: export of C4 Krebs-cycle intermediates from mitochondria. Supporting Evidence: PMID:24395786 by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. |
| GO:0015909 long-chain fatty acid transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Long-chain fatty acid transport (electronic). Reason: As for the fatty-acid transporter activity: fatty-acid flipping linked to proton leak, non-core. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt proton entry into the mitochondrial matrix affecting ATP turnover as a protection mechanism against oxidative stress. |
| GO:0017077 oxidative phosphorylation uncoupler activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Oxidative phosphorylation uncoupler activity (IBA). Reason: UCP2 was named by homology to UCP1, and this IBA follows that name: the donors are UCP1 itself (MGI:98894, RGD:3931) and a plant UCP. Reconstitution and silencing data instead show a C4-dicarboxylate/phosphate antiporter. UniProt also states that UCP2 does not mediate adaptive thermogenesis, though that line is itself a similarity-based assertion (ECO:0000250 from UniProtKB:P70406), so against an IBA it is inference against inference and nothing here turns on it; the reconstitution and silencing data carry the argument. The FA-activated proton conductance is real and is kept separately as GO:0015078, non-core; the difference is that GO:0015078 asserts a transport capability while this term asserts its physiological consequence, that the leak uncouples oxidative phosphorylation. The first is measured, the second is what the UCP1 orthologs do and UCP2 is not shown to. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000642156 SUPPORTS SOURCE BUT NOT TARGET Uncoupler activity grounded in UCP1 (and a plant UCP); UCP2 is instead a C4-dicarboxylate/phosphate antiporter whose uncoupling role is disputed. MGI:MGI:98894 SUPPORTS SOURCE BUT NOT TARGET Thermogenic UCP1 orthologue providing the experimental grounding of the node. RGD:3931 SUPPORTS SOURCE BUT NOT TARGET Thermogenic UCP1 orthologue providing the experimental grounding of the node. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. PMID:24395786 Here we show that UCP2 is a metabolite transporter that regulates substrate oxidation in mitochondria. file:human/UCP2/UCP2-uniprot.txt Does not mediate adaptive thermogenesis |
| GO:0019003 GDP binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GDP binding (electronic). Reason: Purine nucleotides bind the UCP cavity and inhibit proton conductance; a regulatory binding property, not core. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt The GDP-binding domain is located within the hydrophilic cavity, with GDP phosphates likely forming salt bridges with the charged residues, Lys-141 and Arg-185. file:human/UCP2/UCP2-uniprot.txt cardiolipin and long-chain free fatty acids and inhibited by purine nucleotides ATP and ADP. |
| GO:0030225 macrophage differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Macrophage differentiation. Reason: Mouse data: UCP2 limits ROS to sustain itaconate and alternative activation of inflammation-resolving macrophages; context-specific. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0030225 macrophage differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Macrophage differentiation. Reason: Mouse data: UCP2 limits ROS to sustain itaconate and alternative activation of inflammation-resolving macrophages; context-specific. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000107 | MODIFY | Summary: Mitochondrial membrane. Reason: Correct but less specific than the established inner-membrane location, and refined here for the same reason as the GO:0005739 rows in this review. The gene already carries GO:0005743 on seven accepted rows, and GO:0005743 is a confirmed descendant of GO:0031966. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Mitochondrion inner membrane {ECO:0000250|UniProtKB:P70406}; |
| GO:0032869 cellular response to insulin stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0032870 cellular response to hormone stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to hormone stimulus (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0034198 cellular response to amino acid starvation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to amino acid starvation (electronic transfer from rodent data). Reason: Based on changes in UCP2 expression in rodent tissues; altered expression under a condition does not establish that UCP2 carries out part of the response. Over-annotation relative to its transporter function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0042803 protein homodimerization activity | IDA PMID:26182433 A biophysical study on molecular physiology of the uncouplin... | KEEP AS NON CORE | Summary: Protein homodimerization activity (IDA). Reason: Reconstituted UCP2 self-associates and appears to function as a dimer of dimers; a structural property rather than its function. Supporting Evidence: PMID:26182433 collectively suggest that the reconstituted proteins self-associate in the lipid membranes. PMID:33373220 Findings suggest a tetrameric functional form for UCP2. file:human/UCP2/UCP2-uniprot.txt Homotetramer. Adopts an asymmetrical dimer of dimers functional form. |
| GO:0042803 protein homodimerization activity | IDA PMID:33373220 Functional Oligomeric Forms of Uncoupling Protein 2: Strong ... | KEEP AS NON CORE | Summary: Protein homodimerization activity (IDA). Reason: Reconstituted UCP2 self-associates and appears to function as a dimer of dimers; a structural property rather than its function. Supporting Evidence: PMID:26182433 collectively suggest that the reconstituted proteins self-associate in the lipid membranes. PMID:33373220 Findings suggest a tetrameric functional form for UCP2. file:human/UCP2/UCP2-uniprot.txt Homotetramer. Adopts an asymmetrical dimer of dimers functional form. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (electronic). Reason: UCP2 lowers mitochondrial ROS and can protect cells from ROS-induced apoptosis; indirect. Supporting Evidence: PMID:22292025 Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS) accumulation (P<0.001) and apoptosis (P<0.001) compared to the controls when the cells were exposed to hypoxia. |
| GO:0051881 regulation of mitochondrial membrane potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of mitochondrial membrane potential. Reason: UCP2 silencing raises inner-membrane potential and ATP:ADP ratio in glucose-grown cells; an indirect consequence of its transport function. Supporting Evidence: PMID:24395786 showed a higher inner mitochondrial membrane potential and ATP:ADP ratio associated with a lower lactate release. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | TOO GENERAL | Summary: Transmembrane transport. Reason: True of UCP2 but uninformative, because more specific transmembrane-transport terms accepted in this review already entail it - GO:0071423 malate transmembrane transport and GO:1990542 mitochondrial transmembrane transport among them, both confirmed descendants of GO:0055085 in the QuickGO is_a/part_of closure. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0061179 negative regulation of insulin secretion involved in cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of insulin secretion involved in cellular response to glucose stimulus (electronic from mouse). Reason: Ucp2-null mice show hyperinsulinaemic hypoglycaemia and impaired-function UCP2 variants were reported in children with congenital hyperinsulinism, consistent with UCP2 restraining glucose-stimulated secretion by limiting mitochondrial oxidation. The human disease association is disputed and the effect is indirect, so non-core. Supporting Evidence: PMID:19065272 UCP2 knockout mice exhibit an hyperinsulinemic hypoglycemia, suggesting an involvement of UCP2 in insulin secretion. PMID:19065272 Functional assays in yeast and in insulin-secreting cells revealed an impaired activity of UCP2 mutants. |
| GO:0070542 response to fatty acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to fatty acid (electronic transfer from rodent expression/physiology data). Reason: UCP2 expression is induced by this condition in rodent studies, and UCP2 modulates the cellular ROS/metabolic response; an indirect, non-core physiological role rather than its molecular function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0070778 L-aspartate transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: L-aspartate transmembrane transport (inferred from MF). Reason: Consistent with the IDA transport data. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. |
| GO:0071284 cellular response to lead ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to lead ion (electronic transfer from rodent data). Reason: Based on changes in UCP2 expression in rodent tissues; altered expression under a condition does not establish that UCP2 carries out part of the response. Over-annotation relative to its transporter function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0071333 cellular response to glucose stimulus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cellular response to glucose stimulus. Reason: In beta cells and hypothalamic neurons UCP2 dampens glucose-driven mitochondrial ATP production/ROS; supported by mouse studies, but a regulatory consequence rather than core activity. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). |
| GO:0071333 cellular response to glucose stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular response to glucose stimulus. Reason: In beta cells and hypothalamic neurons UCP2 dampens glucose-driven mitochondrial ATP production/ROS; supported by mouse studies, but a regulatory consequence rather than core activity. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). |
| GO:0071423 malate transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: Malate transmembrane transport (inferred from MF). Reason: Consistent with the IDA transport data. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. |
| GO:0071548 response to dexamethasone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to dexamethasone (electronic transfer from rodent data). Reason: Based on changes in UCP2 expression in rodent tissues; altered expression under a condition does not establish that UCP2 carries out part of the response. Over-annotation relative to its transporter function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0072593 reactive oxygen species metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Reactive oxygen species metabolic process. Reason: UCP2 lowers mitochondrial ROS production by limiting Krebs-cycle oxidation (and possibly mild uncoupling); indirect. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0072593 reactive oxygen species metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reactive oxygen species metabolic process. Reason: UCP2 lowers mitochondrial ROS production by limiting Krebs-cycle oxidation (and possibly mild uncoupling); indirect. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. |
| GO:0097421 liver regeneration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Liver regeneration (electronic transfer from rodent data). Reason: Based on changes in UCP2 expression in rodent tissues; altered expression under a condition does not establish that UCP2 carries out part of the response. Over-annotation relative to its transporter function. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:0110099 negative regulation of calcium import into the mitochondrion | IDA PMID:27642082 PRMT1-mediated methylation of MICU1 determines the UCP2/3 de... | UNDECIDED | Summary: Negative regulation of calcium import into the mitochondrion (IDA, PRMT1/MICU1 study). Reason: The abstract states that UCP2/3 normalise the Ca2+ sensitivity of methylated MICU1 and thereby re-establish mitochondrial Ca2+ uptake, which reads as a positive rather than negative effect; the full text, which may report a different condition, was not available, so the direction cannot be adjudicated. Supporting Evidence: PMID:27642082 UCP2/3 normalize Ca(2+) sensitivity of methylated MICU1 and, thus, re-establish mitochondrial Ca(2+) uptake activity. |
| GO:0120162 positive regulation of cold-induced thermogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis. Reason: Loss of UCP2 in mouse brown adipose tissue impairs non-shivering thermogenesis by shifting fuel use toward glucose, an indirect metabolic effect; UCP2 is not itself a thermogenic uncoupler. Supporting Evidence: PMID:28130074 Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue. |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis. Reason: Loss of UCP2 in mouse brown adipose tissue impairs non-shivering thermogenesis by shifting fuel use toward glucose, an indirect metabolic effect; UCP2 is not itself a thermogenic uncoupler. Supporting Evidence: PMID:28130074 Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:28130074 Loss of UCP2 impairs cold-induced non-shivering thermogenesi... | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis. Reason: Loss of UCP2 in mouse brown adipose tissue impairs non-shivering thermogenesis by shifting fuel use toward glucose, an indirect metabolic effect; UCP2 is not itself a thermogenic uncoupler. Supporting Evidence: PMID:28130074 Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue. |
| GO:0140787 phosphate ion uniporter activity | IDA PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | KEEP AS NON CORE | Summary: Phosphate ion uniporter activity (IDA). Reason: UCP2 can unidirectionally transport phosphate in reconstitution; physiologically phosphate moves as the counter-substrate of the antiport. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt anions including L-malate, L-aspartate, phosphate and chloride ions (PubMed:22524567, PubMed:24395786, PubMed:26182433). |
| GO:1902356 oxaloacetate(2-) transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: Oxaloacetate(2-) transmembrane transport (inferred from MF). Reason: Consistent with the IDA transport data. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. |
| GO:1902358 sulfate transmembrane transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Sulfate transmembrane transport (inferred from MF). Reason: In vitro substrate property; non-core. Supporting Evidence: PMID:24395786 UCP2 reconstituted in lipid vesicles catalyzed the exchange of malate, oxaloacetate, and aspartate for phosphate plus a proton from opposite sides of the membrane. |
| GO:1902476 chloride transmembrane transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Chloride transmembrane transport (inferred from MF). Reason: In vitro property; non-core. Supporting Evidence: PMID:22524567 Neuronal UCPs also exhibit transmembrane chloride transport activity. |
| GO:1902600 proton transmembrane transport | TAS PMID:9054939 Uncoupling protein-2: a novel gene linked to obesity and hyp... | KEEP AS NON CORE | Summary: Proton transmembrane transport (TAS, discovery paper). Reason: Original proposal of UCP2 as an uncoupling protein; proton leak is retained as a debated, non-core function. Supporting Evidence: PMID:9054939 In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. |
| GO:1990542 mitochondrial transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial transmembrane transport. Reason: Correct: UCP2 moves metabolites across the inner mitochondrial membrane. Supporting Evidence: PMID:24395786 by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:1990542 mitochondrial transmembrane transport | IMP PMID:24395786 UCP2 transports C4 metabolites out of mitochondria, regulati... | ACCEPT | Summary: Mitochondrial transmembrane transport. Reason: Correct: UCP2 moves metabolites across the inner mitochondrial membrane. Supporting Evidence: PMID:24395786 by exporting C4 compounds out of mitochondria, UCP2 limits the oxidation of acetyl-CoA-producing substrates such as glucose and enhances glutaminolysis, preventing the mitochondrial accumulation of C4 metabolites derived from glutamine. file:human/UCP2/UCP2-uniprot.txt Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. |
| GO:1990845 adaptive thermogenesis | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Adaptive thermogenesis (IBA). Reason: UniProt explicitly records that UCP2 does not mediate adaptive thermogenesis; the IBA reflects the UCP1 thermogenic function at the family node, which UCP2 has not retained. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001183920 SUPPORTS SOURCE BUT NOT TARGET Node grounded only in Ucp1 adaptive thermogenesis; UCP2 does not mediate adaptive thermogenesis. MGI:MGI:98894 SUPPORTS SOURCE BUT NOT TARGET Thermogenic UCP1 orthologue providing the experimental grounding of the node. Supporting Evidence: file:human/UCP2/UCP2-uniprot.txt adaptive thermogenesis (By similarity) |
Loading supporting content…
Download this section (compressed HTML)Q: Do the UCP2 variants reported in congenital hyperinsulinism impair C4-dicarboxylate/phosphate antiport in human beta cells, and is UCP2 haploinsufficiency sufficient to cause hyperinsulinism given that the reported variants were inherited from a parent?
Q: What fraction of UCP2-dependent changes in mitochondrial coupling reflects fatty-acid-activated proton leak versus reduced substrate oxidation caused by C4-metabolite export?
Experiment: Measure malate/aspartate efflux, oxygen consumption and glucose-stimulated insulin secretion in human stem-cell-derived beta cells carrying UCP2 knockout or patient variants, rescued with wild-type or transport-dead UCP2, to test whether the secretion phenotype tracks antiport activity.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)