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Transbilayer lipid diffusion promoted by Bax: implications for apoptosis.

Abstract：

:It is known that the proapoptotic protein Bax facilitates the formation of pores in bilayers, resulting in the release of proteins from the intermitochondrial space. We demonstrate that another consequence of the interaction of Bax with membranes is an increase in the rate of lipid transbilayer diffusion. We use two independent assays for transbilayer diffusion, one involving the formation of asymmetric liposomes by placing a pyrene-labeled lipid into the outer monolayer of preformed vesicles and another assay based on the initial preparation of liposomes having an asymmetric transbilayer distribution of lipids. With both methods we find that oligomeric BaxDeltaC or full-length Bax in the presence of tBid, but not monomeric full-length Bax, strongly promotes the rate of transbilayer diffusion. Although biological membranes exhibit rates of lipid transbilayer diffusion of minutes or less, they are able to maintain an asymmetric distribution of lipids across the bilayer. In the case of mitochondria, cardiolipin is sequestered on the inner leaflet of the inner mitochondrial membrane. However, during apoptosis this lipid translocates to the outer surface of the outer mitochondrial membrane. This phenomenon must involve an increase in the rate of transbilayer diffusion. The results of the present paper demonstrate that an activated form of Bax can cause this increased rate.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Epand RF,Martinou JC,Montessuit S,Epand RM

doi

10.1021/bi035348w

subject

Has Abstract

pub_date

2003-12-16 00:00:00

pages

14576-82

issue

49

eissn

0006-2960

issn

1520-4995

journal_volume

42

pub_type

杂志文章

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