title: Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function.
abstract: 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 approximately 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 (H(2)O(2)) 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 H(2)O(2). Genes with higher expression levels in the mutant, in the presence of H(2)O(2), 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 H(2)O(2). 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.
authors.affiliation: ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Kasuga
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA.
authors.forename: Chaoguang
authors.initials: C
authors.lastname: Tian
authors.affiliation: UFP - Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Lemos
authors.affiliation: UFP - Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Castro
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA.
authors.forename: N Louise
authors.initials: NL
authors.lastname: Glass
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004334:Drug Administration Schedule; D042967:Electron Transport Complex I / Q000172:deficiency; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D050259:Genes, Mitochondrial; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects*; D009492:Neurospora crassa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; C012491:phytosphingosine; D013110:Sphingosine