Release of cytochrome c from liver mitochondria during permeability transition.
The mitochondrial permeability transition (PT) follows opening of megachannels in the inner membrane and may be part of a programmed death pathway. Recently a role for cytochrome c in programmed cell death has been proposed, although its relationship to PT has not been been determined. We studied the release of cytochrome c from liver mitochondria undergoing PT. Well-coupled mitochondria treated with 5 mM atractyloside (ATR) or 100 microM calcium chloride were found to undergo PT and release cytochrome c into the incubation buffer within 5 minutes. Control mitochondria and mitochondria treated with the uncoupler FCCP did not undergo PT or release cytochrome c at 5 or 15 minutes. PT induced by ATR could be prevented by pretreatment with 10 microM cyclosporin A. Mitochondria incubated with ATR or calcium caused a 20-30% decrease in electron transfer rate via cytochrome c and cytochrome c oxidase. We conclude that cytochrome c release is an early event during mitochondrial PT, and is sufficient to decrease electron transfer through the terminal electron transport components of the mitochondrion.
Kantrow
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SP
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Piantadosi
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CA
D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014475:Uncoupling Agents / Q000494:pharmacology
D003574:Cytochrome c Group; D014475:Uncoupling Agents; D001278:Atractyloside; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003576:Electron Transport Complex IV; D002122:Calcium Chloride