Document Detail


Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast.
MedLine Citation:
PMID:  22754872     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ivan Orlandi; Nadia Casatta; Marina Vai
Publication Detail:
Type:  Journal Article     Date:  2012-06-29
Journal Detail:
Title:  Frontiers in oncology     Volume:  2     ISSN:  2234-943X     ISO Abbreviation:  Front Oncol     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-08-23     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  101568867     Medline TA:  Front Oncol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  67     Citation Subset:  -    
Affiliation:
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca Milano, Italy.
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