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

Title
Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function
Type
Article in International Scientific Journal
Year
2009
Authors
kasuga, t
(Author)
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tian, cg
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lemos, c
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castro, a
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glass, nl
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Journal
Title: MicrobiologyImported from Authenticus Search for Journal Publications
Vol. 155
Pages: 3134-3141
ISSN: 1350-0872
Other information
Authenticus ID: P-003-GBE
Abstract (EN): Treatment of Neurospora crassa cells with phytosphingosine (PHS) induces programmed cell death (PCD) 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 similar to 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 (nuo 14) 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.
Language: English
Type (Professor's evaluation): Scientific
Contact: avideira@ibmc.up.pt
No. of pages: 8
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