Cardiolipin provides an essential activating platform for caspase-8 on mitochondria

Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human...

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Bibliographic Details
Published in:The Journal of cell biology 2008-11, Vol.183 (4), p.681-696
Main Authors: Gonzalvez, Francois, Schug, Zachary T, Houtkooper, Riekelt H, MacKenzie, Elaine D, Brooks, David G, Wanders, Ronald J.A, Petit, Patrice X, Vaz, Frédéric M, Gottlieb, Eyal
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Apoptosis - physiology
Barth syndrome
Cardiolipins
Cardiolipins - genetics
Cardiolipins - metabolism
Caspase 8 - genetics
Caspase 8 - metabolism
Cell death
Cell growth
Cell lines
Cells
Cytochromes
fas Receptor - genetics
fas Receptor - metabolism
HeLa Cells
Humans
Lipids
Liposomes
Medical disorders
Membranes
Mitochondria
Mitochondria - enzymology
Mitochondria - metabolism
Mitochondrial Membranes - enzymology
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Protein Transport - physiology
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary:Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human disorder Barth syndrome. Using Barth syndrome patient-derived cells and HeLa cells in which tafazzin was knocked down, we show that cardiolipin is required for apoptosis in the type II mitochondria-dependent response to Fas stimulation. Cardiolipin provides an anchor and activating platform for caspase-8 translocation to, and embedding in, the mitochondrial membrane, where it oligomerizes and is further activated, steps that are necessary for an efficient type II apoptotic response.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200803129