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.
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September 1999
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Conference Article|
September 01 1999
Ceramide induces cytochrome c release from isolated mitochondria
Christoph Richter;
Christoph Richter
1
1Laboratorium für Biochemie I, Eidgenössische Technische Hochschule (ETH), Universitätstr. 16, CH-8092 Zürich, Switzerland
1To whom correspondence should be addressed.
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Pedram Ghafourifar
Pedram Ghafourifar
1Laboratorium für Biochemie I, Eidgenössische Technische Hochschule (ETH), Universitätstr. 16, CH-8092 Zürich, Switzerland
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 1999 The Biochemical Society
1999
Biochem Soc Symp (1999) 66: 27–31.
Citation
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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