Ceramide induces cytochrome c release from isolated mitochondria.
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 (delta psi m) 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 delta psi m, 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.
Richter
C
C
Laboratorium für Biochemie I, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland.
Ghafourifar
P
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002518:Ceramides / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D051381:Rats
D002518:Ceramides; D003574:Cytochrome c Group