Genetic and biocheminal atudy on the function of cardiolipin in mammlian cells

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Phosphatidylglycerophosphate (PGP) synthase catalyzes a reaction involved in the synthesis of phosphatidylglycerol which serves as a metablic precursor for cardiolipin found exclusively in mitochondrial membranes of eukaryotic cells. We isolated a Chinese hamster ovary cell mutant with temperature-dependent defects both in PGP synthase adtivity in vitro and in the synthesis of phosphatidylglycerol and cardiolipin in vivo, together with temperature-sensitivity for cell growth. When phosphatidylglycerol and cardiolipin levels were reduced, this mutant possessed not only morphological but also functional abnormalities of mitochondria, manifested by reduced oxygen consumption and ATP production, increased glycolysis, and more stringent temperature-sensitivity for cell growth in glucose-deficientmedium. These results constitute genetic evidence that PGP synthase is essential for cell growth and that cardiolipin plays a critical rote in mitochondrial functions.