Document Detail


Yeast cells lacking the CIT1-encoded mitochondrial citrate synthase are hypersusceptible to heat- or aging-induced apoptosis.
MedLine Citation:
PMID:  17615299     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In Saccharomyces cerevisiae, the initial reaction of the tricarboxylic acid cycle is catalyzed by the mitochondrial citrate synthase Cit1. The function of Cit1 has previously been studied mainly in terms of acetate utilization and metabolon construction. Here, we report the relationship between the function of Cit1 and apoptosis. Yeast cells with cit1 deletion showed a temperature-sensitive growth phenotype, and they displayed a rapid loss in viability associated with typical apoptotic hallmarks, i.e., reactive oxygen species (ROS) accumulation and nuclear fragmentation, DNA breakage, and phosphatidylserine translocation, when exposed to heat stress. On long-term cultivation, cit1 null strains showed increased potentials for both aging-induced apoptosis and adaptive regrowth. Activation of the metacaspase Yca1 was detected during heat- or aging-induced apoptosis in cit1 null strains, and accordingly, deletion of YCA1 suppressed the apoptotic phenotype caused by cit1 null mutation. Cells with cit1 deletion showed higher tendency toward glutathione (GSH) depletion and subsequent ROS accumulation than the wild type, which was rescued by exogenous GSH, glutamate, or glutathione disulfide (GSSG). These results led us to conclude that GSH deficiency in cit1 null cells is caused by an insufficient supply of glutamate necessary for biosynthesis of GSH rather than the depletion of reducing power required for reduction of GSSG to GSH.
Authors:
Yong Joo Lee; Kwang Lae Hoe; Pil Jae Maeng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-05
Journal Detail:
Title:  Molecular biology of the cell     Volume:  18     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-24     Completed Date:  2007-11-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3556-67     Citation Subset:  IM    
Affiliation:
Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University, 305-764 Daejeon, Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis* / drug effects
Biological Markers / metabolism
Biological Transport / drug effects
Caspases / antagonists & inhibitors
Citrate (si)-Synthase / deficiency*
DNA Fragmentation / drug effects
Enzyme Inhibitors / pharmacology
Gene Deletion
Glutamates / metabolism
Glutathione / metabolism
Heat-Shock Response / drug effects
Hot Temperature*
Mitochondria / drug effects,  enzymology*
Phenotype
Phosphatidylserines / metabolism
Reactive Oxygen Species / metabolism
Saccharomyces cerevisiae / cytology*,  drug effects,  enzymology*,  growth & development
Saccharomyces cerevisiae Proteins / antagonists & inhibitors
Time Factors
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Enzyme Inhibitors; 0/Glutamates; 0/Phosphatidylserines; 0/Reactive Oxygen Species; 0/Saccharomyces cerevisiae Proteins; 70-18-8/Glutathione; EC 2.3.3.1/Citrate (si)-Synthase; EC 3.4.22.-/Caspases; EC 3.4.22.-/MCA1 protein, S cerevisiae
Comments/Corrections

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