Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

摘要: It has been known for a long time that mitochondria isolated from hepatocytes treated with glucagon or Ca2+-mobilizing agents such as phenylephrine show an increase in their adenine nucleotide (AdN) content, respiratory activity, and calcium retention capacity (CRC). Here, we have studied the role of SCaMC-3/slc25a23, mitochondrial ATP-Mg/Pi carrier present adult mouse liver, control AdN levels respiration response to Ca2+ signals candidate target actions. With use SCaMC-3 knock-out (KO) mice, found is responsible accumulation AdNs liver strictly Ca2+-dependent way S0.5 activation 3.3 ± 0.9 μm. Accumulation matrix allows SCaMC-3-dependent CRC. In addition, required acquire fully active state 3 AdN-depleted mitochondria, although further not followed by increases respiration. Moreover, addition oligomycin-sensitive oxygen consumption maximal rates cells derived wild type, but SCaMC-3-KO mice administration vivo results CRC type mice. These oxidative phosphorylation observed agents, possibly allowing Ca2+, events permissive other