Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia.

ABSTRACT: Anoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in the mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extent in isolated mitochondria in real-time, we demonstrate that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. ¹³C metabolic tracing or untargeted analysis of metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system showed that NAD⁺ regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase Complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP),

SUBMITTER: Ravasz D 

PROVIDER: S-EPMC10798963 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature