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PMID: 20850011 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization.

Cell ·Vol. 142 ·No. 6 ·2010-09-17 ·Pages 889-901

Montessuit S, Somasekharan SP, Terrones O, Lucken-Ardjomande S, Herzig S, Schwarzenbacher R, Manstein DJ, Bossy-Wetzel E, Basañez G, Meda P, Martinou JC

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.

MeSH Terms
Amino Acid Sequence Animals Apoptosis BH3 Interacting Domain Death Agonist Protein/metabolism Cardiolipins/metabolism Cell-Free System Dynamins GTP Phosphohydrolases/metabolism HeLa Cells Humans Liposomes/metabolism Microtubule-Associated Proteins/metabolism Mitochondrial Membranes/metabolism Mitochondrial Proteins/metabolism Models, Molecular Molecular Sequence Data Rats bcl-2-Associated X Protein/metabolism
Chemicals
BH3 Interacting Domain Death Agonist Protein Cardiolipins Liposomes Microtubule-Associated Proteins Mitochondrial Proteins bcl-2-Associated X Protein GTP Phosphohydrolases DNM1L protein, human Dynamins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Montessuit Sylvie
Department of Cell Biology, University of Geneva, Sciences III, 30 quai Ernest Ansermet, 1211 Geneva 4, Switzerland.
Somasekharan Syam Prakash
Terrones Oihana
Lucken-Ardjomande Safa
Herzig Sébastien
Schwarzenbacher Robert
Manstein Dietmar J
Bossy-Wetzel Ella
Basañez Gorka
Meda Paolo
Martinou Jean-Claude
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.08.017
Published
2010-09-17
Pages
889-901
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4115189
Subset
IM
Grants
NINDS NIH HHS · R01 NS055193 · United States
NINDS NIH HHS · R01 NS0474556 · United States
NEI NIH HHS · R01 EY016164 · United States
NINDS NIH HHS · R01 NS047456 · United States
NEI NIH HHS · EY016164 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2010.08.017 PMC Full Text View journal details
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