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

被引：346

作者：

Montessuit, Sylvie ^{[1
]}

Somasekharan, Syam Prakash ^{[1
]}

Terrones, Oihana ^{[1
]}

Lucken-Ardjomande, Safa ^{[1
]}

Herzig, Sebastien ^{[1
]}

Schwarzenbacher, Robert ^{[2
]}

Manstein, Dietmar J. ^{[3
]}

Bossy-Wetzel, Ella ^{[4
]}

Basanez, Gorka ^{[5
]}

Meda, Paolo ^{[6
]}

Martinou, Jean-Claude ^{[1
]}

机构：

[1] Univ Geneva, Dept Cell Biol, CH-1211 Geneva 4, Switzerland

[2] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria

[3] Hannover Med Sch, Inst Biophys Chem, D-30625 Hannover, Germany

[4] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA

[5] Univ Pais Vasco Euskal Herriko Unibertsitatea, CSIC, Ctr Mixto, Unidad Biofis, Bilbao 48080, Spain

[6] Ctr Med Univ Geneva, Dept Cell Physiol & Metab, CH-1211 Geneva 4, Switzerland

来源：

CELL | 2010年 / 142卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

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

D O I：

10.1016/j.cell.2010.08.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：889 / 901

页数：13

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