Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function

Cardiolipin (CL) is a unique phospholipid which is present throughout the e ukaryotic kingdom and is localized in mitochondrial membranes. Saccharomyce s cerevisiae cells containing a disruption of CRD1, the structural gene enc oding CL synthase, have no CL in mitochondrial membranes. To elucidate the physiological role of CL, we compared mitochondrial functions in the crd1 D elta mutant and isogenic wild type. The crd1 Delta mutant loses viability a t elevated temperature, and prolonged culture at 37 degrees C leads to loss of the mitochondrial genome. Mutant membranes have increased phosphatidylg lycerol (PG) when grown in a nonfermentable carbon source but have almost n o detectable PG; in medium containing glucose. In glucose-grown cells, maxi mum respiratory rate, ATPase and cytochrome oxidase activities, and protein import are deficient in the mutant. The ADP/ATP carrier is defective even during growth in a nonfermentable carbon source. The mitochondrial membrane potential is decreased in mutant cells. The decrease is more pronounced in glucose-grown cells, which lack PG;, but is also apparent in membranes con taining PC: (i.e. in nonfermentable carbon sources). We propose that CL is required for maintaining the mitochondrial membrane potential and that redu ced membrane potential in the absence of CL leads to defects in protein imp ort and other mitochondrial functions.