title: Cardiolipin is not required to maintain mitochondrial DNA stability or cell viability for Saccharomyces cerevisiae grown at elevated temperatures.
abstract: In eukaryotic cells, the phospholipid cardiolipin (CL) is primarily found in the inner mitochondrial membrane. Saccharomyces cerevisiae mutants, unable to synthesize CL because of a null allele of the CRD1 gene (encodes CL synthase), have been reported with different phenotypes. Some mutants, when grown on a nonfermentable carbon source at elevated temperatures, exhibit mitochondrial DNA instability, loss of viability, and significant defects in several functions that rely on the mitochondrial energy transducing system (ETS). These mutants also lack the immediate precursor to CL, phosphatidylglycerol (PG), when grown on glucose as a carbon source. Other mutants show reduced growth efficiency on a nonfermentable carbon source but much milder phenotypes associated with growth at elevated temperatures and increased levels of PG when grown on glucose. We present evidence that mitochondrial DNA instability, loss of viability, and defects in the ETS exhibited at elevated temperatures by some mutants are caused by the reduced expression of the PET56 gene in the presence of the his3 Delta 200 allele and not the lack of CL alone. We also found that PG is present and elevated in all crd1 Delta strains when grown on glucose. A supermolecular complex between complex III and complex IV of the mitochondrial ETS detected in wild type cells was missing in all of the above crd1 Delta cells. The level of components of the ETS was also reduced in crd1 Delta cells grown at elevated temperatures because of reduced gene expression and not reduced stability. These results suggest that all phenotypes reported for cells carrying the his3 Delta 200 allele and lacking CL should be re-evaluated.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Su
authors.forename: Eugenia
authors.initials: E
authors.lastname: Mileykovskaya
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Amoscato
authors.forename: William
authors.initials: W
authors.lastname: Dowhan
mesh_terms: D001483:Base Sequence; D002308:Cardiolipins / Q000737:chemistry / Q000494:pharmacology*; D017931:DNA Primers; D004271:DNA, Fungal / Q000187:drug effects / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D006358:Hot Temperature; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010715:Phosphatidylglycerols / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D013696:Temperature
chemical_list: D002308:Cardiolipins; D017931:DNA Primers; D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D010715:Phosphatidylglycerols