Nitric oxide and mitochondria.
Nitric oxide (NO) and its derivatives (reactive nitrogen species) have multiple effects on mitochondria that impact on cell physiology and cell death. Mitochondria may produce and consume NO and NO stimulates mitochondrial biogenesis, apparently via cGMP upregulation of transcriptional factors. NO inhibits mitochondrial respiration via: (A) an acute and reversible inhibition of cytochrome oxidase by NO in competition with O2, and (B) irreversible inhibition of multiple sites by reactive nitrogen species. NO is a potent vasodilator (via cGMP), increasing O2 and respiratory substrate supply to mitochondria. NO stimulates reactive oxygen and nitrogen species production from mitochondria via respiratory inhibition, reaction with ubiquinol and reaction with O2 in the membrane. NO can induce apoptosis, mainly via oxidative stress. NO induces necrosis, mainly via energy depletion. Reactive nitrogen species activation of the mitochondrial permeability transition pore may cause apoptosis or necrosis. NO may protect against mitochondria-mediated cell death by multiple mechanisms.
Brown
Guy C
GC
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom. gcb@mole.bio.cam.ac.uk
D017209:Apoptosis; D019069:Cell Respiration; D003576:Electron Transport Complex IV / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D003576:Electron Transport Complex IV