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

    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

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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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