Caspase-8 goes cardiolipin: a new platform to provide mitochondria with microdomains of apoptotic signals?
In certain cell types, apoptosis in response to extracellular stimuli like Fas depends on a mitochondrial amplificatory loop: the apical caspase-8 cleaves and activates the BH3-only member of the Bcl-2 family BID. In turn, BID induces the release of cytochrome c from mitochondria to the cytoplasm, where it is required to fully activate effector caspases. In this issue of The Journal of Cell Biology, Gonzalvez et al. (see p. 681) show that when caspase-8 activation and production of functional BID is required, it is performed on mitochondrial platforms provided by the mitochondrion-specific lipid cardiolipin. Cardiolipin anchors caspase-8 at contact sites between inner and outer mitochondrial membranes, facilitating its self activation. These findings suggests that like other second messengers such as Ca(2+) and cAMP, production of apoptotic messengers can be compartmentalized in close proximity to their intracellular target.
Scorrano
Luca
L
Deptartment of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland. luca.scorrano@unige.ch
D000217:Acyltransferases; D017209:Apoptosis / Q000502:physiology*; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D002308:Cardiolipins; C491901:FAS protein, human; D024101:Mitochondrial Proteins; D014157:Transcription Factors; D019014:fas Receptor; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; C505530:CASP8 protein, human; D053181:Caspase 8