UNIGE document Scientific Article
previous document  unige:20263  next document
add to browser collection

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

Schwarzenbacher, Robert
Manstein, Dietmar J.
Bossy-Wetzel, Ella
show hidden authors show all authors [1 - 11]
Published in Cell. 2010, vol. 142, no. 6, p. 889-901
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.
Keywords Amino Acid SequenceAnimalsApoptosisBH3 Interacting Domain Death Agonist Protein/metabolismCardiolipins/metabolismCell-Free SystemGTP Phosphohydrolases/metabolismHeLa CellsHumansLiposomes/metabolismMicrotubule-Associated Proteins/metabolismMitochondrial Membranes/metabolismMitochondrial Proteins/metabolismModels, MolecularMolecular Sequence DataRatsBcl-2-Associated X Protein/metabolism
PMID: 20850011
Full text
Article (Published version) (1.3 MB) - public document Free access
(ISO format)
MONTESSUIT, Sylvie et al. Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization. In: Cell, 2010, vol. 142, n° 6, p. 889-901. doi: 10.1016/j.cell.2010.08.017 https://archive-ouverte.unige.ch/unige:20263

616 hits



Deposited on : 2012-04-30

Export document
Format :
Citation style :