**12.3. Tyrosine kinases and regulation of mitochondrial functions in ischemia/reperfusion**

Tyrosine phosphorylation is a crucial mechanism for regulating mitochondrial functions [19, 42]. Tyrosine kinases of the Src family (Lyn, Lck, c-Src, Fyn, and Fgr) localize to mitochondria by binding to specific anchoring proteins present in mitochondria [19, 42]. The primary known role of tyrosine phosphorylation is the regulation of the respiratory chain by c-Src [19]. Phosphorylations of NDUFB10 subunit of complex I at Y193, succinate dehydrogenase of complex II at Y215, and subunit II of complex IV on unknown tyrosine by Src increase activities of complexes I, II, and IV [19, 31, 42]. Targeting of c-Src to mitochondria enhances ΔΨm and oxidative phosphorylation in a c-Src-dependent manner [19]. Src and Lck phosphorylate ANT1 at Y194 and reduce ischemic injury in preconditioned cardiac cells [54]. Mitochondrial Fgr kinase phosphorylates complex II, which increases complex II activity and regulates NADH/ FADH2 balance in mitochondria [32]. Epidermal growth factor receptor (EGFR) translocates to mitochondria when phosphorylated on Y845 by Src [43]. EFR interacts with and phosphorylates subunit II of complex IV thereby decreasing its activity and cellular ATP levels [19, 140].

In conclusions, translocation of protein kinases to mitochondria regulates mitochondrial functions in various disease states including ischemia and reperfusion in major organs such as the brain, heart, and kidneys. These findings suggest that these protein kinases can serve as potential effective therapeutic targets to maintain mitochondrial integrity and functions and prevent or reduce organ damage in these disease states.
