Regulation of mitochondrial processes by protein S-nitrosylation

• Published in: Biochimica et biophysica acta Vol. 1820; no. 6; pp. 712 - 721
• Main Author: Piantadosi, Claude A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2012
• Subjects: Animals; Cysteine - chemistry; Cysteine - metabolism; enzymatic reactions; glutathione; Glutathione - chemistry; Glutathione - metabolism; Guanylate Cyclase; heme; Humans; ischemia; mammals; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; NADH dehydrogenase (ubiquinone); neurodegenerative diseases; Nitric oxide; Nitric Oxide - metabolism; Nitrosation; Oxidation-Reduction; Oxidative Phosphorylation; permeability; post-translational modification; proteins; reactive oxygen species; Reactive Oxygen Species - metabolism; Respiration; S-nitrosation; S-Nitrosothiols - metabolism; S-nitrosylation; Signal Transduction; S-nitrosation; Mitochondria; Metabolism; Respiration; Nitric oxide; S-nitrosylation
• ISSN: 0304-4165; 0006-3002; 1872-8006; 0006-3002
• DOI: 10.1016/j.bbagen.2011.03.008

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. 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. 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. 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. ► Mitochondria contain both S-nitrosylating and denitrosylating mechanisms. ► Reversible protein S-nitrosylation supports redox regulation in mitochondria. ► SNO inhibits Complex I and steps in intermediary and fatty acid metabolism. ► SNO activates mitochondrial protein importation and regulates mitochondrial fission. ► Mitochondrial SNO proteins are involved in both cell protection and cell damage.