Regulation of mitochondrial processes by protein S-nitrosylation.

BACKGROUND: Nitric oxide (NO) exerts powerful physiological effects through guanylate cyclase (GC), a non-mitochondrial enzyme, and through the generation of protein cysteinyl-NO (SNO) adducts-a post-translational modification relevant to mitochondrial biology. A small number of SNO proteins, generated by various mechanisms, are characteristically found in mammalian mitochondria and influence the regulation of oxidative phosphorylation and other aspects of mitochondrial function. SCOPE OF REVIEW: The principles by which mitochondrial SNO proteins are formed and their actions, independently or collectively with NO binding to heme, iron-sulfur centers, or to glutathione (GSH) are reviewed on a molecular background of SNO-based signal transduction. MAJOR CONCLUSIONS: Mitochondrial SNO-proteins have been demonstrated to inhibit Complex I of the electron transport chain, to modulate mitochondrial reactive oxygen species (ROS) production, influence calcium-dependent opening of the mitochondrial permeability transition pore (MPTP), promote selective importation of mitochondrial protein, and stimulate mitochondrial fission. The ease of reversibility and the affirmation of regulated S-nitros(yl)ating and denitros(yl)ating enzymatic reactions support hypotheses that SNO regulates the mitochondrion through redox mechanisms. SNO modification of mitochondrial proteins, whether homeostatic or adaptive (physiological), or pathogenic, is an area of active investigation. GENERAL SIGNIFICANCE: Mitochondrial SNO proteins are associated with mainly protective, bur some pathological effects; the former mainly in inflammatory and ischemia/reperfusion syndromes and the latter in neurodegenerative diseases. Experimentally, mitochondrial SNO delivery is also emerging as a potential new area of therapeutics. This article is part of a Special Issue entitled: Regulation of cellular processes by S-nitrosylation.

Duke Scholars

Author Claude Anthony Piantadosi Medicine, Pulmonary, Allergy, and Critical Care Medicine