Novel Mechanism Discovered for Communication Between Proteins That Cause ‘cell Suicide’
ScienceDaily (Sep. 27, 2010) — A recent study undertaken by investigators at five research centres, amongst which is the CSIC-University of the Basque Country Biophysics Unit, provides new clues for the understanding of the 'cell suicide' process.
The research was published in the latest issue of the journal Cell.
Our bodies daily eliminate in a controlled manner more than 100 million defective cells, by means of a procedure known as 'cell suicide' or apoptosis. This is a highly complicated process, any imbalances thus arising causing serious diseases, prominent amongst which is cancer. Over the past two decades it has been possible to identify various cellular components involved in apoptosis. Nevertheless, there are still important unresolved questions about the functioning of certain key elements in this great cell riddle.
This study has revealed that three essential components of the apoptotic process, the BAX and DRP-1 proteins and cardiolipin, act in a joint manner to produce a large hole in the external membrane of the mitochondria, proving to be lethal for the cell.
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Read more here/Leia mais aqui: Science Daily
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Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization
Cell, Volume 142, Issue 6, 889-901, 17 September 2010
Copyright © 2010 Elsevier Inc. All rights reserved.
10.1016/j.cell.2010.08.017
Authors
Sylvie Montessuit,Syam Prakash Somasekharan,Oihana Terrones,Safa Lucken-Ardjomande,Sébastien Herzig,Robert Schwarzenbacher,Dietmar J. Manstein,Ella Bossy-Wetzel,Gorka Basañez,Paolo Meda,Jean-Claude Martinou
Highlights
Drp1 promotes tBid-induced Bax oligomerization by triggering membrane hemifusion
Drp1 induces membrane hemifusion independently of its GTPase activity
Cardiolipin is essential for Drp1-induced membrane hemifusion
Drp1 mutants lacking membrane hemifusion activity delay Bax oligomerization in vivo
Summary
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.
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