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

J. Biol. Chem., Vol. 283, Issue 9, 5622-5631, February 29, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/9/5622    most recent M709147200v1 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 Churbanova, I. Y. Articles by Sevrioukova, I. F. Search for Related Content PubMed PubMed Citation Articles by Churbanova, I. Y. Articles by Sevrioukova, I. F. Social Bookmarking                      What's this?

Redox-dependent Changes in Molecular Properties of Mitochondrial Apoptosis-inducing Factor^*

From the Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900

Mitochondrial apoptosis-inducing factor (AIF) is a central player in the caspase-independent cell death pathway whose normal physiological function remains unclear. Our study showed that naturally folded mouse AIF very slowly reacts with NAD(P)H (k_cat of 0.2-0.01 s^-1) forming tight, dimeric, and air-stable FADH₂-NAD(P) charge-transfer complexes ineffective in electron transfer. FAD reduction is accompanied by a conformational change involving AIF-specific N-terminal and regulatory 509–559 peptides and the active site His⁴⁵³, and it affects susceptibility of AIF to calpain and AIF-DNA interaction, the two events critical for initiating caspase-independent apoptosis. Based on our results, we propose that formation of long lived complexes with NAD(P)H and redox reorganization may be functionally important and enable AIF to act as a redox-signaling molecule linking NAD(P)H-dependent metabolic pathways to apoptosis.

Received for publication, November 7, 2007 , and in revised form, December 24, 2007.

^* This work was supported by National Institutes of Health Grant GM67637. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text, Figs. 1S–6S, and references.

¹ To whom correspondence should be addressed: Dept. of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine, CA 92697-3900. Tel.: 949-824-1953; Fax: 949-824-3280; E-mail: sevrioui{at}uci.edu.

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