Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displays lipid 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 its truncated form, tBid, to mitochondria to facilitate the release of apoptogenic cytochrome c. The mechanism of Bid relocation to mitochondria was unclear. We report here novel biochemical evidence indicating that Bid has lipid transfer activity between mitochondria and other intracellular membranes, thereby explaining its dynamic relocation to mitochondria. First, physiological concentrations of phospholipids such as phosphatidic acid and phosphatidylglycerol induced an accumulation of full-length Bid in mitochondria when incubated with light membranes enriched in endoplasmic reticulum. Secondly, native and recombinant Bid, as well as tBid, displayed lipid transfer activity 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 phospholipids. We discuss how this new role of Bid may relate to its proapoptotic action.
Esposti
M D
MD
Cancer Research Campaign Molecular Pharmacology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. mauro1it@hotmail.com
Erler
J T
JT
Hickman
J A
JA
Dive
C
C
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D050356:Lipid Metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494815:Bid protein, mouse; D002352:Carrier Proteins; D003574:Cytochrome c Group; D010743:Phospholipids; D011994:Recombinant Proteins