Nitric oxide: orchestrating hypoxia regulation through mitochondrial respiration and the endoplasmic reticulum stress response.
Mitochondria have long been considered to be the powerhouse of the living cell, generating energy in the form of the molecule ATP via the process of oxidative phosphorylation. In the past 20 years, it has been recognised that they also play an important role in the implementation of apoptosis, or programmed cell death. More recently it has become evident that mitochondria also participate in the orchestration of cellular defence responses. At physiological concentrations, the gaseous molecule nitric oxide (NO) inhibits the mitochondrial enzyme cytochrome c oxidase (complex IV) in competition with oxygen. This interaction underlies the mitochondrial actions of NO, which range from the physiological regulation of cell respiration, through mitochondrial signalling, to the development of "metabolic hypoxia" -- a situation in which, although oxygen is available, the cell is unable to utilise it.
Xu
Weiming
W
Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, Gower Street, London, WC1E 6BT, UK.
Charles
Ian G
IG
Moncada
Salvador
S
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D019069:Cell Respiration; D003576:Electron Transport Complex IV / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D015398:Signal Transduction
D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D010100:Oxygen; D002118:Calcium