Journal
JOURNAL OF CELL BIOLOGY
Volume 183, Issue 4, Pages 681-696Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200803129
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Funding
- Cancer Research UK
- Prinses Beatrix Fonds [WAR05-0126]
- Barth Syndrome Foundation
- Association Francaise contre les Myophaties [11557]
- National Institute of Child Health and Human Development Mental Retardation Research Center [HD-2406]
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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.
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