| Phosphatidate phosphatase activity plays key role in protection against fatty acid-induced toxicity in yeast. | |
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MedLine Citation:
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PMID: 21708942 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The PAH1-encoded phosphatidate (PA) phosphatase in Saccharomyces cerevisiae is a pivotal enzyme that produces diacylglycerol for the synthesis of triacylglycerol (TAG) and simultaneously controls the level of PA used for phospholipid synthesis. Quantitative lipid analysis showed that the pah1Δ mutation caused a reduction in TAG mass and an elevation in the mass of phospholipids and free fatty acids, changes that were more pronounced in the stationary phase. The levels of unsaturated fatty acids in the pah1Δ mutant were unaltered, although the ratio of palmitoleic acid to oleic acid was increased with a similar change in the fatty acid composition of phospholipids. The pah1Δ mutant exhibited classic hallmarks of apoptosis in stationary phase and a marked reduction in the quantity of cytoplasmic lipid droplets. Cells lacking PA phosphatase were sensitive to exogenous fatty acids in the order of toxicity palmitoleic acid > oleic acid > palmitic acid. In contrast, the growth of wild type cells was not inhibited by fatty acid supplementation. In addition, wild type cells supplemented with palmitoleic acid exhibited an induction in PA phosphatase activity and an increase in TAG synthesis. Deletion of the DGK1-encoded diacylglycerol kinase, which counteracts PA phosphatase in controlling PA content, suppressed the defect in lipid droplet formation in the pah1Δ mutant. However, the sensitivity of the pah1Δ mutant to palmitoleic acid was not rescued by the dgk1Δ mutation. Overall, these findings indicate a key role of PA phosphatase in TAG synthesis for protection against fatty acid-induced toxicity. |
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Authors:
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Stylianos Fakas; Yixuan Qiu; Joseph L Dixon; Gil-Soo Han; Kelly V Ruggles; Jeanne Garbarino; Stephen L Sturley; George M Carman |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-06-27 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-15 Completed Date: 2011-10-19 Revised Date: 2012-09-26 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 29074-85 Citation Subset: IM |
Affiliation:
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Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology Fatty Acids / metabolism* Mutation Phosphatidate Phosphatase / genetics, metabolism* Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae Proteins / genetics, metabolism* Triglycerides / biosynthesis*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK-007647/DK/NIDDK NIH HHS; DK-54320/DK/NIDDK NIH HHS; GM-28140/GM/NIGMS NIH HHS; R37 GM028140-30/GM/NIGMS NIH HHS; RR-021120/RR/NCRR NIH HHS; RR-02415803/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Saccharomyces cerevisiae Proteins; 0/Triglycerides; EC 3.1.3.4/Phosphatidate Phosphatase; EC 3.1.3.4/SMP2 protein, S cerevisiae |
| Comments/Corrections | |
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