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Biochem Biophys Res Commun. 1997 Mar 27;232(3):669-71.

Release of cytochrome c from liver mitochondria during permeability transition.

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Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.


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.

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