Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death
| Autor: | Ana Castro, Catarina L. Lemos, N. Louise Glass, Artur Falcão, Arnaldo Videira |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Programmed cell death
Mutant Apoptosis DNA Fragmentation Biology Biochemistry Neurospora crassa Fungal Proteins Mitochondrial Proteins Sphingosine Fragmentation (cell biology) Molecular Biology chemistry.chemical_classification Reactive oxygen species Electron Transport Complex I fungi Apoptosis Inducing Factor Hydrogen Peroxide Cell Biology biology.organism_classification Molecular biology Cell biology Metabolism and Bioenergetics Mitochondrial respiratory chain chemistry Mutation DNA fragmentation |
| Zdroj: | Journal of Biological Chemistry. 283:19314-19321 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m802112200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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