spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 7 October 2008
doi: 10.1242/jcs.029587

Journal of Cell Science 121, 3515-3523 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.029587v1
121/21/3515    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Lartigue, L.
Right arrow Articles by De Giorgi, F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lartigue, L.
Right arrow Articles by De Giorgi, F.

Short Report

An intracellular wave of cytochrome c propagates and precedes Bax redistribution during apoptosis

Lydia Lartigue1,*, Chantal Medina1,*, Laura Schembri1, Paul Chabert1, Marion Zanese1,2, Flora Tomasello1, Renée Dalibart1, Didier Thoraval3, Marc Crouzet3, François Ichas1,2,{ddagger} and Francesca De Giorgi1,2

1 INSERM U916, Université Bordeaux 2, Institut Bergonié, 229 cours de l'Argonne, 33000 Bordeaux, France
2 FLUOFARMA, 2 rue Robert Escarpit, 33600 Pessac, France
3 CNRS UMR 5095, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France

{ddagger} Author for correspondence (e-mail: francois.ichas{at}inserm.fr)

Accepted 21 July 2008

Summary

Bax is considered to be pivotal in inducing cytochrome c release (CCR) from mitochondria during apoptosis. Indeed, Bax redistributes to the mitochondrial outer membrane (MOM) upon activation and forms homo-multimers that are capable of permeabilizing the MOM. Our attempts to image this sequence of events in single live cells resulted in unexpected observations. Bax redistribution exhibited two distinct components: an early minor redistribution that was silent in terms of homo-multimerization and a major late redistribution that was synchronous with the formation of Bax multimers, but that proceeded belatedly, i.e. only after caspase 3/7 (C3/7) had already been activated. Intriguingly, neither of these two components of redistribution correlated with CCR, which turned out to be spatially organized, propagating as a traveling wave at constant velocity. Strikingly, propagation of the CCR wave (1) preceded signs of in situ Bax conformational activation; (2) appeared to be independent of autocatalytic loops involving a positive feedback of either C3/7, Ca2+ mobilization or mitochondrial permeability transition; and (3) was triggered by diffuse stimulation with the synthetic Bak activator BH3I-1 but then proceeded independently of Bak activation. Thus, the CCR wave not only questions the exact role of Bax redistribution in cell death, but also indicates the existence of yet unidentified positive-feedback loops that ensure a spatiotemporal control of apoptosis at the subcellular scale.

Key words: Bax, Apoptosis, Caspase 3, Cytochrome c, Recombinant probes, Single-cell imaging






© The Company of Biologists Ltd 2008