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

J. Biol. Chem., Vol. 283, Issue 28, 19314-19321, July 11, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/28/19314    most recent M802112200v1 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 Castro, A. Articles by Videira, A. Search for Related Content PubMed PubMed Citation Articles by Castro, A. Articles by Videira, A. Social Bookmarking                      What's this?

Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death^*

Ana Castro, Catarina Lemos, Artur Falcão, N. Louise Glass^¶, and Arnaldo Videira^||1

From the IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal, the UFP - Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal, the ^¶Department of Plant and Microbial Biology, University of California, Berkeley, California 94720-3102, and the ^||ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal

We have studied the effects of phytosphingosine (PHS) on cells of the filamentous fungus Neurospora crassa. Highly reduced viability, impairment of asexual spore germination, DNA condensation and fragmentation, and production of reactive oxygen species were observed in conidia treated with the drug, suggesting that PHS induces an apoptosis-like death in this fungus. Interestingly, we found that complex I mutants are more resistant to PHS treatment than the wild type strain. This effect appears to be specific because it was not observed in mutants defective in other components of the mitochondrial respiratory chain, pointing to a particular involvement of complex I in cell death. The response of the mutant strains to PHS correlated with their response to hydrogen peroxide. The fact that complex I mutants generate fewer reactive oxygen species than the wild type strain when exposed to PHS likely explains the PHS-resistant phenotype. As compared with the wild type strain, we also found that a strain containing a deletion in the gene encoding an AIF (apoptosis-inducing factor)-like protein is more resistant to PHS and H₂O₂. In contrast, a strain containing a deletion in a gene encoding an AMID (AIF-homologous mitochondrion-associated inducer of death)-like polypeptide is more sensitive to both drugs. These results indicate that N. crassa has the potential to be a model organism to investigate the molecular basis of programmed cell death in eukaryotic species.

Received for publication, March 17, 2008 , and in revised form, May 7, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant RO1 GM60468 (to N. L. G.). This work was also supported by research grants from Fundação para a Ciência e a Tecnologia from Portugal and the Programa Operacional Ciência, Tecnologia, Inovação program of QCA III (co-participated by Fundo Europeu de Desenvolvimento Regional) and by a sabbatical fellowship from Fundação Luso-Americana. 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 two supplemental figures.

¹ To whom correspondence should be addressed. Tel.: 35-1-226074900; Fax: 35-1-226099157; E-mail: avideira{at}ibmc.up.pt.

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