Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration.
Human mitochondrial respiration is distinct from that of most plants, microorganisms and even some metazoans in that it reduces molecular oxygen only through the highly cyanide-sensitive enzyme cytochrome c oxidase. Here we show that expression of the cyanide-insensitive alternative oxidase (AOX), recently identified in the ascidian Ciona intestinalis, is well tolerated by cultured human cells and confers spectacular cyanide resistance to mitochondrial substrate oxidation. The expressed AOX seems to be confined to mitochondria. AOX involvement in electron flow is triggered by a highly reduced redox status of the respiratory chain (RC) and enhanced by pyruvate; otherwise, the enzyme remains essentially inactive. AOX expression promises to be a valuable tool to limit the deleterious consequences of RC deficiency in human cells and whole animals.
Hakkaart
Gerrit A J
GA
Institute of Medical Technology and Tampere University Hospital, University of Tampere, Tampere, Finland.
Dassa
Emmanuel P
EP
Jacobs
Howard T
HT
Rustin
Pierre
P
D000818:Animals; D002460:Cell Line; D019069:Cell Respiration / Q000502:physiology*; D003486:Cyanides / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010940:Plant Proteins; D000099188:Alternative Oxidase
D003486:Cyanides; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010100:Oxygen; D010940:Plant Proteins; D000099188:Alternative Oxidase