Established Principles and Emerging Concepts on the Interplay between Mitochondrial Physiology and S-(De)nitrosylation: Implications in Cancer and Neurodegeneration
Effects of NO and nitrosative stress on mitochondrial electron transfer chain. NO, namely, the fraction produced in the cytosol by NOS, can cross cell membranes (e.g., the mitochondrial outer and inner membranes) and reversibly or irreversibly modifies mitochondrial complexes of the electron transfer chain (ETC). Specifically, nitration of all complexes, nitrosylation of Fe-heme-containing cytochrome c oxidase (C IV), generation of dinitrosyl iron complexes of Fe-S centers (e.g., those present in the Complex I), and S-nitrosylation of Complex I, III, IV, F0/F1 ATPase, as well as other unspecified mitochondrial proteins are shown. These modifications negatively affect ETC efficiency, and ATP production and decrease mitochondrial transmembrane potential ), which represents e crucial event upstream of several mitochondrial functions, such as mitochondrial dynamics, mitophagy, and apoptosis.