Caspase-8 goes cardiolipin: A new platform to provide mitochondria with microdomains of apoptotic signals?

Abstract

In certain cell types, apoptosis in response to extracellular stimuli like Fas depends on a mitochondrial amplifi catory 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-specifi c lipid cardiolipin. Cardiolipin anchors caspase-8 at contact sites between inner and outer mitochondrial membranes, facilitating its self activation. These fi ndings suggests that like other second messengers such as Ca2+ and cAMP, production of apoptotic messengers can be compartmentalized in close proximity to their intracellular target. © 2008 Scorrano.