| Lipid droplet formation protects against gluco/lipotoxicity in Candida parapsilosis: An essential role of fatty acid desaturase Ole1. | |
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MedLine Citation:
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PMID: 21897120 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Elevated levels of glucose and lipids can result in cellular dysfunction in eukaryotic cells ranging from Saccharomyces cerevisiae yeasts to human cells. Moreover, glucotoxicity and lipotoxicity can cause cell death, although the mechanism(s) for lethality is unclear. In the present study, we utilized Candida parapsilosis fatty acid desaturase (OLE1) and fatty acid synthase (FAS2) gene deletion mutants and wild-type (WT) yeast cells to unravel the relationship to glucose and lipid induced cell death in eukaryotic cells. Incubation of WT yeast cells with glucose led to the rapid accumulation of lipid droplets, whereas lipid droplet formation was severely impaired in yeast cells with deletion of OLE1 (ole1∆/∆) or FAS2 (fas2∆/∆). Interestingly, ole1∆/∆ yeast cells died within hours in a 1% glucose medium without fatty acid supplementation, whereas the WT or fas2∆/∆ yeast cells did not. In glucose medium, ole1∆/∆ yeast cells accumulated saturated fatty acids, while fas2∆/∆ did not. Addition of saturated fatty acids (e.g. palmitic acid) enhanced ole1∆/∆ yeast cell death, whereas the addition of unsaturated fatty acids (e.g. oleic or palmitoleic acid) rescued cell death. Furthermore, palmitic acid and glucose medium induced apopotic cell death in ole1∆/∆ yeast cells, which was dependent on mitochondrial function. Thus, our results show that glucotoxicity is directly linked to lipotoxicity, which we demonstrate is mediated by mitochondrial function. |
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Authors:
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Long Nam Nguyen; Joshua D Nosanchuk |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-15 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 10 ISSN: 1551-4005 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Albert Einstein College of Medicine; Bronx, NY USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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