Caspase-8 and Bid: Caught in the act between death receptors and mitochondria

► We describe the role of mitochondria in caspase-8 signalling. ► Polyubiquitination of caspase-8 at the DISC modulates its activation. ► The cardiolipin enriched “mitosome” is a new activation platform for caspase-8. ► MTCH2/MIMP facilitates the recruitment of active tBid to the mitochondria. ► The type I/type II cell discrimination is also due to differences on XIAP levels.