**5. Succinate-ubiquinone oxidoreductase (complex II)**

Complex II is an essential regulator of metabolic reprogramming and respiratory adaptation. Mitochondrial Src-type tyrosine kinase Fgr phosphorylates complex II on Y535, Y596, and Y604 when activated by ROS generated by I/R [32]. Phosphorylation of Y604 on the flavoprotein subunit of succinate dehydrogenase (FpSDH) increases activity of complex II and serves as a metabolic adaptation to increased ROS production [32, 34]. Fgr-mediated phosphorylation also reduces the protein levels of complex I, which alters the mitochondrial preference for fuel oxidation from NADH to FADH2 , which increases the metabolic capacity of mitochondria to utilize alternative fuels when complex I is impaired [32]. Blocking phosphorylation of FpSDH on Y604 abolishes the capacity of mitochondria to adapt their metabolism after hypoxia/reoxygenation [32]. Mitochondrial phosphatases dephosphorylate Y604 and reverse this metabolic adaptation [32, 34]. In contrast, phosphorylation of FpSDH in cancer cells undergoing hypoxia decreases and dephosphorylation of FpSDH increases SDH activity [35]. Our data show that the activity of complex II in injured renal proximal tubular cells (RPTC) and in the ischemic kidney cortex is unchanged, whereas the activity of complex I is decreased [25, 36]. Supplementing the RPTC with succinate (complex II substrate) ameliorates mitochondrial dysfunction, ATP deficits, oxidative stress, and cell death after injury associated with the generation of ROS and oxidative stress [36].
