Document Detail

Loss of cardiolipin leads to longevity defects that are alleviated by alterations in stress response signaling.
MedLine Citation:
PMID:  19401462     Owner:  NLM     Status:  MEDLINE    
Perturbation of cardiolipin (CL) synthesis in yeast cells leads to defective respiratory chain function and mitochondrial DNA loss, both of which have been implicated in aging in mammals. The availability of yeast CL mutants enabled us to directly investigate the role of CL synthesis in aging. In this report, we show that the replicative life span of pgs1Delta, which lacks both CL and the precursor phosphatidylglycerol (PG), was significantly decreased at 30 degrees C. The life span of crd1Delta, which has PG but not CL, was unaffected at 30 degrees C but reduced at 37 degrees C. Life span extension induced by calorie restriction was not affected by the loss of CL. However, mild heat and osmotic stress, which extend life span in wild type cells, did not increase longevity in CL mutants, suggesting that the stress response is perturbed in these mutants. Consistent with this, longevity defects in pgs1Delta were alleviated by down-regulation of the high osmolarity glycerol stress response pathway, as well as by promoting cell integrity with the osmotic stabilizer sorbitol or via genetic suppression with the kre5(W1166X) mutant. These findings show for the first time that perturbation of CL synthesis leads to decreased longevity in yeast, which is restored by altering signaling through stress response pathways.
Jingming Zhou; Quan Zhong; Guiling Li; Miriam L Greenberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-04-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-10-27     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18106-14     Citation Subset:  IM    
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
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MeSH Terms
CDPdiacylglycerol-Serine O-Phosphatidyltransferase / genetics,  metabolism
Cardiolipins / biosynthesis,  metabolism*
Down-Regulation / physiology
Heat-Shock Response / physiology
Mitochondria / metabolism
Mitogen-Activated Protein Kinases / genetics,  metabolism
Osmotic Pressure / physiology
Phosphatidylglycerols / metabolism
Saccharomyces cerevisiae / genetics,  growth & development*,  physiology*
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Signal Transduction / physiology*
Stress, Physiological / physiology*
Grant Support
Reg. No./Substance:
0/Cardiolipins; 0/Phosphatidylglycerols; 0/Saccharomyces cerevisiae Proteins; EC 2.7.10.-/HOG1 protein, S cerevisiae; EC Protein Kinases; EC O-Phosphatidyltransferase; EC protein, S cerevisiae

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