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

This Article Full Text Full Text (PDF) Supplementary table All Versions of this Article: mic.0.029710-0v1 155/9/3134    most recent Alert me when this article is cited 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 Citing Articles Citing Articles via CrossRef Google Scholar Articles by Videira, A. Articles by Glass, N. L. PubMed PubMed Citation Articles by Videira, A. Articles by Glass, N. L. Agricola Articles by Videira, A. Articles by Glass, N. L.

Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

¹ IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal
² ICBAS – Instituto de Ciências Biomédicas de Abel Salazar, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal
³ Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA
⁴ UFP – Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal

Treatment of Neurospora crassa cells with phytosphingosine (PHS) induces programmed cell death (PCD) by an unknown mechanism. To determine the relationship between PHS treatment and PCD, we determined changes in global gene expression levels in N. crassa during a time-course of PHS treatment. Most genes having differential expression levels compared to untreated samples showed an increase in relative expression level upon PHS exposure. However, genes encoding mitochondrial proteins were highly enriched among 100 genes that showed a relative decrease in expression levels after PHS treatment, suggesting that repression of these genes might be related to the death-inducing effects of PHS. Since mutants in respiratory chain complex I are more resistant to both PHS and hydrogen peroxide (H₂O₂) than the wild-type strain, possibly related to the production of reactive oxygen species, we also compared gene expression profiles of a complex I mutant (nuo14) and wild-type in response to H₂O₂. Genes with higher expression levels in the mutant, in the presence of H₂O₂, are also significantly enriched in genes encoding mitochondrial proteins. These data suggest that complex I mutants cope better with drug-induced decrease in expression of genes encoding mitochondrial proteins and may explain their increased resistance to both PHS and H₂O₂. As a way of identifying new components required for PHS-induced death, we analysed the PHS sensitivity of 24 strains carrying deletions in genes that showed a significant alteration in expression pattern when the wild-type was exposed to the sphingolipid. Two additional mutants showing increased resistance to PHS were identified and both encode predicted mitochondrial proteins, further supporting the role of the mitochondria in PHS-induced PCD.

Correspondence
Arnaldo Videira
avideira{at}ibmc.up.pt

The microarray data associated with this paper have been deposited at the Yale Microarray Experimental Design site (http://www.yale.edu/townsend/Links/ffdatabase/introduction.html) under Experiment ID 48.

A supplementary table showing mRNA profiling results and functional annotations is available with the online version of this paper.