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

Abstract

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.