| Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast. | |
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MedLine Citation:
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PMID: 22754872 Owner: NLM Status: PubMed-not-MEDLINE |
Abstract/OtherAbstract:
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ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality. |
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Authors:
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Ivan Orlandi; Nadia Casatta; Marina Vai |
Publication Detail:
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Type: Journal Article Date: 2012-06-29 |
Journal Detail:
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Title: Frontiers in oncology Volume: 2 ISSN: 2234-943X ISO Abbreviation: Front Oncol Publication Date: 2012 |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-08-23 Revised Date: 2012-09-27 |
Medline Journal Info:
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Nlm Unique ID: 101568867 Medline TA: Front Oncol Country: Switzerland |
Other Details:
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Languages: eng Pagination: 67 Citation Subset: - |
Affiliation:
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Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca Milano, Italy. |
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