IDH2-mediated regulation of the biogenesis of the oxidative phosphorylation system.

Several subunits in the matrix domain of mitochondrial complex I (CI) have been posited to be redox sensors for CI, but how elevated levels of reactive oxygen species (ROS) impinge on CI assembly is unknown. We report that genetic disruption of the mitochondrial NADPH-generating enzyme, isocitrate dehydrogenase 2 (IDH2), in flight muscles results in elevated ROS levels and impairment of assembly of the oxidative phosphorylation system (OXPHOS). Mechanistically, this begins with an inhibition of biosynthesis of the matrix domain of CI and progresses to involve multiple OXPHOS complexes.

Insights from Drosophila on mitochondrial complex I.

NADH:ubiquinone oxidoreductase, more commonly referred to as mitochondrial complex I (CI), is the largest discrete enzyme of the oxidative phosphorylation system (OXPHOS). It is localized to the mitochondrial inner membrane. CI oxidizes NADH generated from the tricarboxylic acid cycle to NAD, in a series of redox reactions that culminates in the reduction of ubiquinone, and the transport of protons from the matrix across the inner membrane to the intermembrane space.