Loss of the mitochondrial lipid cardiolipin leads to decreased glutathione synthesis.

Previous studies demonstrated that loss of CL in the yeast mutant crd1? leads to perturbation of mitochondrial iron?sulfur (FeS) cluster biogenesis, resulting in decreased activity of mitochondrial and cytosolic Fe-S-requiring enzymes, including aconitase and sulfite reductase. In the current study, we show that crd1? cells exhibit decreased levels of glutamate ...
and cysteine and are deficient in the essential antioxidant, glutathione, a tripeptide of glutamate, cysteine, and glycine. Glutathione is the most abundant non-protein thiol essential for maintaining intracellular redox potential in almost all eukaryotes, including yeast. Consistent with glutathione deficiency, the growth defect of crd1? cells at elevated temperature was rescued by supplementation of glutathione or glutamate and cysteine. Sensitivity to the oxidants iron (FeSO4) and hydrogen peroxide (H2O2), was rescued by supplementation of glutathione. The decreased intracellular glutathione concentration in crd1? was restored by supplementation of glutamate and cysteine, but not by overexpressing YAP1, an activator of expression of glutathione biosynthetic enzymes. These findings show for the first time that CL plays a critical role in regulating intracellular glutathione metabolism.
Mesh Terms:
Cardiolipins, Cysteine, Ferrous Compounds, Glutamic Acid, Glutathione, Hydrogen Peroxide, Membrane Proteins, Mitochondria, Oxidative Stress, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transferases (Other Substituted Phosphate Groups)
Biochim Biophys Acta Mol Cell Biol Lipids
Date: Dec. 01, 2019
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