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Molecular and Cellular Biology, October 2006, p. 7397-7408, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.02282-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibiting the Mitochondrial Fission Machinery Does Not Prevent Bax/Bak-Dependent Apoptosis{dagger}

Philippe A. Parone,1 Dominic I. James,1,{ddagger} Sandrine Da Cruz,1 Yves Mattenberger,1 Olivier Donzé,1,§ François Barja,1,2 and Jean-Claude Martinou1*

Department of Cell Biology, University of Geneva, Quai Ernest-Ansermet 30, Geneva, Switzerland,1 Département de botanique et de biologie végétale, 10 chemin des embrouchis, 1254 Jussy, Switzerland2

Received 29 November 2005/ Returned for modification 3 January 2006/ Accepted 17 July 2006

Apoptosis, induced by a number of death stimuli, is associated with a fragmentation of the mitochondrial network. These morphological changes in mitochondria have been shown to require proteins, such as Drp1 or hFis1, which are involved in regulating the fission of mitochondria. However, the precise role of mitochondrial fission during apoptosis remains elusive. Here we report that inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down-regulating of Drp1 or hFis1, prevents the fragmentation of the mitochondrial network and partially inhibits the release of cytochrome c from the mitochondria but fails to block the efflux of Smac/DIABLO. In addition, preventing mitochondrial fragmentation does not inhibit cell death induced by Bax/Bak-dependent death stimuli, in contrast to the effects of Bcl-xL or caspase inhibition. Therefore, the fission of mitochondria is a dispensable event in Bax/Bak-dependent apoptosis.

* Corresponding author. Mailing address: Department of Cell Biology, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland. Phone: 41 22 702 64 43. Fax: 41 22 702 64 42. E-mail: Jean-Claude.Martinou{at}cellbio.unige.ch.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Cell Regulation Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, United Kingdom.

§ Present address: APOTECH Corporation, Ch. des Croisettes 22, CH-1066 Epalinges, Switzerland.

Molecular and Cellular Biology, October 2006, p. 7397-7408, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.02282-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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