Cardiolipin (CL) has recently been shown to provide an anchor and an essential activating platform for caspase-8 on mitochondria. We hypothesize that these platforms may correspond to "raft-like" microdomains, which have demonstrated to be detectable on mitochondrial membrane of cells undergoing apoptosis. The role for CL in "raft-like" microdomains could be to anchor caspase-8 at contact sites between inner and outer membranes, facilitating its self-activation, Bid cleavage and apoptosis execution. The role played by "raft-like" microdomains in the apoptotic program could introduce a new task in the pathogenetic studies on human diseases associated with cardiolipin dismetabolism. (c) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.