title: Increased resistance of complex I mutants to phytosphingosine-induced programmed cell death.
abstract: 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.
authors.affiliation: 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.forename: Catarina
authors.initials: C
authors.lastname: Lemos
authors.forename: Artur
authors.initials: A
authors.lastname: Falcão
authors.forename: N Louise
authors.initials: NL
authors.lastname: Glass
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051033:Apoptosis Inducing Factor; D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; C012491:phytosphingosine; D013110:Sphingosine