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Mol. Cell. Biol. 21 (21): 7268-7276
Copyright © 2001 by the American Society for Microbiology. All rights reserved.
Molecular and Cellular Biology, November 2001, p. 7268-7276, Vol. 21, No. 21
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7268-7276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Bid, a Widely Expressed Proapoptotic Protein of the
Bcl-2 Family, Displays Lipid Transfer Activity
Mauro Degli
Esposti,1,*
Janine T.
Erler,1
John A.
Hickman,2 and
Caroline
Dive1
Cancer Research Campaign Molecular
Pharmacology Group, School of Biological Sciences, University of
Manchester, Manchester M13 9PT, United Kingdom,1
and Institut de Recherches Servier, Suresnes 92150, Paris,
France2
Received 16 July 2001/Accepted 13 August 2001
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 phosphatidylgycerol 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.
*
Corresponding author. Mailing address: CRC
Molecular Pharmacology Group, School of Biological Sciences,
University of Manchester, Stopford Building, Oxford
Road, Manchester M13 9PT, United Kingdom. Phone: 44 161 2755484. Fax: 44 161 2755600. E-mail: mauro1it{at}hotmail.com.
Molecular and Cellular Biology, November 2001, p. 7268-7276, Vol. 21, No. 21
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7268-7276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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