UCP2

Dicarboxylate carrier SLC25A8

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. Continuous export of oxaloacetate and related four-carbon dicarboxylates from mitochondrial matrix into the cytosol negatively regulates the oxidation of acetyl-CoA substrates via the Krebs cycle, lowering the ATP/ADP ratio and reactive oxygen species (ROS) production (PubMed:24395786). May mediate inducible proton entry into the mitochondrial matrix affecting ATP turnover as a protection mechanism against oxidative stress. The proton currents are most likely associated with fatty acid flipping across the inner membrane of mitochondria in a metabolic process regulated by free fatty acids and purine nucleotides (By similarity) (PubMed:11171965, PubMed:11278935, PubMed:22524567, PubMed:26182433, PubMed:33373220). Regulates the use of glucose as a source of energy. Required for glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). This mitochondrial adaptation mechanism modulates the VMH pool of glucose-excited neurons with an impact on systemic glucose homeostasis (By similarity). Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. Attenuates ROS production in response to IL33 to preserve the integrity of the Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (By similarity). Can unidirectionally transport anions including L-malate, L-aspartate, phosphate and chloride ions (PubMed:22524567, PubMed:24395786, PubMed:26182433). Does not mediate adaptive thermogenesis (By similarity)