Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols.
NO or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial complex I by several different mechanisms that are not well characterised. There is an inactivation by NO, peroxynitrite and S-nitrosothiols that is reversible by light or reduced thiols, and therefore may be due to S-nitrosation or Fe-nitrosylation of the complex. There is also an irreversible inhibition by peroxynitrite, other oxidants and high levels of NO, which may be due to tyrosine nitration, oxidation of residues or damage of iron sulfur centres. Inactivation of complex I by NO or RNS is seen in cells or tissues expressing iNOS, and may be relevant to inflammatory pathologies, such as septic shock and Parkinson's disease.
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. gcb@mole.bio.cam.ac.uk
Guy C
GC
Brown
Vilmante
V
Borutaite
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D015538:Nitrosation; D009603:Nitroso Compounds / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D007506:Iron-Sulfur Proteins; D009603:Nitroso Compounds; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D014443:Tyrosine; D000255:Adenosine Triphosphate; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D042967:Electron Transport Complex I