HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 12, 9029-9041, March 23, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/12/9029    most recent M607614200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Matarrese, P. Articles by Fiorentini, C. Search for Related Content PubMed PubMed Citation Articles by Matarrese, P. Articles by Fiorentini, C. Social Bookmarking                      What's this?

Clostridium difficile Toxin B Causes Apoptosis in Epithelial Cells by Thrilling Mitochondria

INVOLVEMENT OF ATP-SENSITIVE MITOCHONDRIAL POTASSIUM CHANNELS^*

Paola Matarrese¹, Loredana Falzano¹, Alessia Fabbri, Lucrezia Gambardella, Claudio Frank, Blandine Geny, Michel R. Popoff, Walter Malorni², and Carla Fiorentini²³

From the Department of Drug Research and Evaluation, Istituto Superiore di Sanita', Viale Regina Elena 299, 00161 Rome, Italy and the Unite des Toxines Microbiennes, Institut Pasteur, 75724 Paris, Cedex 15, France

Targeting to mitochondria is emerging as a common strategy that bacteria utilize to interact with these central executioners of apoptosis. Several lines of evidence have in fact indicated mitochondria as specific targets for bacterial protein toxins, regarded as the principal virulence factors of pathogenic bacteria. This work shows, for the first time, the ability of the Clostridium difficile toxin B (TcdB), a glucosyltransferase that inhibits the Rho GTPases, to impact mitochondria. In living cells, TcdB provokes an early hyperpolarization of mitochondria that follows a calcium-associated signaling pathway and precedes the final execution step of apoptosis (i.e. mitochondria depolarization). Importantly, in isolated mitochondria, the toxin can induce a calcium-dependent mitochondrial swelling, accompanied by the release of the proapoptogenic factor cytochrome c. This is consistent with a mitochondrial targeting that does not require the Rho-inhibiting activity of the toxin. Of interest, the mitochondrial ATP-sensitive potassium channels are also involved in the apoptotic response to TcdB and appear to be crucial for the cell death execution phase, as demonstrated by using specific modulators of these channels. To our knowledge, the involvement of these mitochondrial channels in the ability of a bacterial toxin to control cell fate is a hitherto unreported finding.

Received for publication, August 9, 2006 , and in revised form, November 30, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² Both authors are principal investigators.

³ To whom correspondence should be addressed. Tel.: 39-0649903006; Fax: 39-0649903691; E-mail: carla.fiorentini{at}iss.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?