Document Detail


Loss of mitochondrial DNA in the yeast cardiolipin synthase crd1 mutant leads to up-regulation of the protein kinase Swe1p that regulates the G2/M transition.
MedLine Citation:
PMID:  20086012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anionic phospholipid cardiolipin and its precursor phosphatidylglycerol are synthesized and localized in the mitochondrial inner membrane of eukaryotes. They are required for structural integrity and optimal activities of a large number of mitochondrial proteins and complexes. Previous studies showed that loss of anionic phospholipids leads to cell inviability in the absence of mitochondrial DNA. However, the mechanism linking loss of anionic phospholipids to petite lethality was unclear. To elucidate the mechanism, we constructed a crd1Deltarho degrees mutant, which is viable and mimics phenotypes of pgs1Delta in the petite background. We found that loss of cardiolipin in rho degrees cells leads to elevated expression of Swe1p, a morphogenesis checkpoint protein. Moreover, the retrograde pathway is activated in crd1Deltarho degrees cells, most likely due to the exacerbation of mitochondrial dysfunction. Interestingly, the expression of SWE1 is dependent on retrograde regulation as elevated expression of SWE1 is suppressed by deletion of RTG2 or RTG3. Taken together, these findings indicate that activation of the retrograde pathway leads to up-regulation of SWE1 in crd1Deltarho degrees cells. These results suggest that anionic phospholipids are required for processes that are essential for normal cell division in rho degrees cells.
Authors:
Shuliang Chen; Dongmei Liu; Russell L Finley; Miriam L Greenberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-29     Completed Date:  2010-05-14     Revised Date:  2011-07-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10397-407     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cardiolipins / metabolism
Cell Division
DNA, Fungal / genetics,  metabolism
DNA, Mitochondrial / genetics*
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Fungal*
Membrane Proteins / genetics,  metabolism*
Mitochondria / physiology*
Mutation / genetics
Phospholipids / analysis
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae / genetics,  growth & development,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Transferases (Other Substituted Phosphate Groups) / genetics,  metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL62263/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiolipins; 0/DNA, Fungal; 0/DNA, Mitochondrial; 0/Membrane Proteins; 0/Phospholipids; 0/RNA, Messenger; 0/Saccharomyces cerevisiae Proteins; 0/Swd1 protein, S cerevisiae; EC 2.7.8.-/Transferases (Other Substituted Phosphate Groups); EC 2.7.8.-/cardiolipin synthetase
Comments/Corrections

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