Title

Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization

Authors

Authors

S. Montessuit; S. P. Somasekharan; O. Terrones; S. Lucken-Ardjomande; S. Herzig; R. Schwarzenbacher; D. J. Manstein; E. Bossy-Wetzel; G. Basanez; P. Meda;J. C. Martinou

Comments

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Abbreviated Journal Title

Cell

Keywords

CYTOCHROME-C RELEASE; BCL-2 FAMILY-MEMBERS; MITOCHONDRIAL; OUTER-MEMBRANE; CELL-DEATH; APOPTOTIC PROTEINS; FISSION; FUSION; PERMEABILIZATION; ACTIVATION; ASSOCIATION; Biochemistry & Molecular Biology; Cell Biology

Abstract

In response to many apoptotic stimuli, oligomerization of Bax is essential for mitochondrial outer membrane permeabilization and the ensuing release of cytochrome c. These events are accompanied by mitochondrial fission that appears to require Drp1, a large GTPase of the dynamin superfamily. Loss of Drp1 leads to decreased cytochrome c release by a mechanism that is poorly understood. Here we show that Drp1 stimulates tBid-induced Bax oligomerization and cytochrome c release by promoting tethering and hemifusion of membranes in vitro. This function of Drp1 is independent of its GTPase activity and relies on arginine 247 and the presence of cardiolipin in membranes. In cells, overexpression of Drp1 R247A/E delays Bax oligomerization and cell death. Our findings uncover a function of Drp1 and provide insight into the mechanism of Bax oligomerization.

Journal Title

Cell

Volume

142

Issue/Number

6

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

889

Last Page

901

WOS Identifier

WOS:000281855000012

ISSN

0092-8674

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