Absence of cardiolipin results in temperature sensitivity, respiratory defects, and mitochondrial DNA instability independent of pet56

J Biol Chem. 2004 Jul 30;279(31):32294-300. doi: 10.1074/jbc.M403275200. Epub 2004 May 29.


Cardiolipin (CL) is a dimeric phospholipid localized primarily in the mitochondrial membrane. Previous studies have shown that yeast cells containing a disruption of CRD1, the structural gene encoding CL synthase, exhibit temperature-sensitive colony formation and multiple mitochondrial defects. A recent report (Zhang, M., Su, X., Mileykovskaya, E., Amoscato, A. A., and Dowhan, W. (2003) J. Biol. Chem. 278, 35204-35210) suggested that defects associated with CL deficiency may result from the reduced expression of PET56 in crd1 Delta mutant backgrounds and should be reevaluated. In the current study, we present evidence that CL deficiency leads to mitochondrial DNA instability, loss of viability, and defects in oxidative phosphorylation at elevated temperatures. The observed mutant phenotypes are characteristic of crd1 Delta mutant cells of both PET56 and pet56 backgrounds and are complemented by an episomal copy of CRD1 but not by expression of the PET56 gene. Phosphatidylglycerol is elevated in crd1 Delta mutant cells when grown in the presence of fermentable and non-fermentable carbon sources, although the extent of the increase is higher in nonfermentable medium. An increase in the ratio of phosphatidylethanolamine to phosphatidylcholine was also apparent in the mutant. These findings demonstrate that CRD1, independent of PET56, is required for optimal mitochondrial function and for an essential cellular function at elevated temperatures.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Blotting, Northern
  • Cardiolipins / genetics
  • Cardiolipins / physiology*
  • Cation Transport Proteins / genetics
  • Cell Division
  • Cell Survival
  • Cloning, Molecular
  • Copper Transport Proteins
  • DNA, Mitochondrial / genetics*
  • Fungal Proteins / genetics
  • Genotype
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methyltransferases / genetics
  • Methyltransferases / physiology*
  • Mutation
  • Oxygen / metabolism
  • Phenotype
  • Phosphatidylcholines / metabolism
  • Phosphatidylglycerols / metabolism
  • Phospholipids / metabolism
  • Phosphorylation
  • Plasmids / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Temperature
  • Time Factors
  • Transferases (Other Substituted Phosphate Groups) / genetics
  • Transferases (Other Substituted Phosphate Groups) / metabolism


  • ATP-Binding Cassette Transporters
  • Cardiolipins
  • Cation Transport Proteins
  • Copper Transport Proteins
  • DNA, Mitochondrial
  • Fungal Proteins
  • Membrane Proteins
  • Phosphatidylcholines
  • Phosphatidylglycerols
  • Phospholipids
  • Saccharomyces cerevisiae Proteins
  • MRM1 protein, S cerevisiae
  • Methyltransferases
  • Transferases (Other Substituted Phosphate Groups)
  • cardiolipin synthetase
  • CRD1 protein, Candida albicans
  • Oxygen