Involvement of cardiolipin in tBID-induced activation of BAX during apoptosis

•Mitochondrial permeabilization during apoptosis is controlled by the BCL-2 family.•BAX and BID are two important pro-apoptotic members of the BCL-2 protein family.•During apoptosis, BAX and BID are activated and recruited to mitochondria.•The mitochondrial phospholipid cardiolipin seems to be involved in these processes.•Evidences for and against are discussed.

Permeabilization of the outer mitochondrial membrane constitutes an essential step in response to a wide range of apoptotic stimuli. Pro-apoptotic members of the BCL-2 family such as BAX and BAK are responsible for disrupting the integrity of the mitochondrial outer membrane, thereby allowing the release of apoptogenic factors including cytochrome c, which activate caspases in the cytosol. How BAX and BAK are activated during apoptosis is still not fully understood. Cooperation between tBID and the mitochondrial-specific phospholipid cardiolipin has been suggested to promote BAX or BAK oligomerization. Here we review the evidence for and against a role for cardiolipin in BAX and BAK activation and in the subsequent onset of apoptosis.