Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displayslipid transfer activity

Bid is an abundant proapoptotic protein of the Bcl-2 family that is crucial for the induction of death receptor-mediated apoptosis in primary tissues such as liver. Bid action has been proposed to involve the relocation of it s truncated form, tBid, to mitochondria to facilitate the release of apopto genic cytochrome c. The mechanism of Bid relocation to mitochondria was unc lear. We report here novel biochemical evidence indicating that Bid has lip id transfer activity between mitochondria and other intracellular membranes , thereby explaining its dynamic relocation to mitochondria. First, physiol ogical concentrations of phospholipids such as phosphatidic acid and phosph atidylgycerol induced an accumulation of full-length Bid in mitochondria wh en incubated with light membranes enriched in endoplasmic reticulum. Second ly, native and recombinant Bid, as well as tBid, displayed lipid transfer a ctivity under the same conditions and at the same nanomolar concentrations leading to mitochondrial relocation and release of cytochrome c. Thus, Bid is likely to be involved in the transport and recycling of mitochondrial ph ospholipids. We discuss how this new role of Bid may relate to its proapopt otic action.