This chapter addresses the role of mitochondria in apoptosis. Emphasis is put on the recently observed influence of ceramides on mitochondrial functions. We report here that N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and, to a much lesser extent, C2-dihydroceramide, induce cytochrome c (cyt c) release from isolated rat liver mitochondria. Ceramide-induced cyt c release is prevented by a low concentration of Bcl-2. The release takes place when cyt c is oxidized, but not when it is reduced. Upon cyt c release mitochondrial oxygen consumption, mitochondrial transmembrane potential (ΔΨm) and Ca2+ retention are diminished. Bcl-2 prevents, and addition of cyt c reverses, the alteration of these mitochondrial functions. In ATP-energized mitochondria ceramides do not alter ΔΨm, neither when cyt c is oxidized nor when it is reduced. This rules out a non-specific disturbance by ceramides of mitochondrial-membrane integrity. It is concluded that some of the apoptogenic properties of ceramides are mediated via their interaction with mitochondrial cyt c followed by its release.
Ceramide induces cytochrome c release from isolated mitochondria
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Guy C. Brown, David G. Nicholls, Chris E. Cooper, Christoph Richter, Pedram Ghafourifar; Ceramide induces cytochrome c release from isolated mitochondria. Biochem Soc Symp 1 September 1999; 66 27–31. doi: https://doi.org/10.1042/bss0660027
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