Ceramide Induces Cytochrome c Release from Isolated Mitochondria IMPORTANCE OF MITOCHONDRIAL REDOX STATE

作者: Pedram Ghafourifar , Sabine D. Klein , Olivier Schucht , Ursula Schenk , Martin Pruschy

DOI: 10.1074/JBC.274.10.6080

关键词: RedoxMitochondrial apoptosis-induced channelCell biologyInner mitochondrial membraneMembrane potentialCytochrome cCeramideOxygenMitochondrionBiology

摘要: Abstract In the present study we show thatN-acetylsphingosine (C2-ceramide),N-hexanoylsphingosine (C6-ceramide), and, to a much lesser extent, C2-dihydroceramide induce cytochromec (cyto c) release from isolated rat liver mitochondria. Ceramide-induced cyto c is prevented by preincubation of mitochondria with low concentration (40 nm) Bcl-2. The takes place when cytoc oxidized but not it reduced. Upon loss, mitochondrial oxygen consumption, transmembrane potential (ΔΨ), and Ca2+ retention are diminished. Incubation Bcl-2 prevents, addition reverses alteration these functions. ATP-energized mitochondria, ceramides do alter ΔΨ, neither nor reduced, ruling out nonspecific disturbance membrane integrity. Furthermore, decrease reducibility cytoc. We conclude that apoptogenic properties in part mediated via their interaction followed its redox state influences detachment ceramide inner membrane.

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