Abstract
Cardiolipin (CL) is a unique phospholipid which is present throughout the eukaryotic kingdom and is localized in mitochondrial membranes. Saccharomyces cerevisiae cells containing a disruption of CRD1, the structural gene encoding CL synthase, have no CL in mitochondrial membranes. To elucidate the physiological role of CL, we compared mitochondrial functions in the crd1Delta mutant and isogenic wild type. The crd1Delta mutant loses viability at elevated temperature, and prolonged culture at 37 degrees C leads to loss of the mitochondrial genome. Mutant membranes have increased phosphatidylglycerol (PG) when grown in a nonfermentable carbon source but have almost no detectable PG in medium containing glucose. In glucose-grown cells, maximum 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 containing PG (i.e. in nonfermentable carbon sources). We propose that CL is required for maintaining the mitochondrial membrane potential and that reduced membrane potential in the absence of CL leads to defects in protein import and other mitochondrial functions.
Highlights
Cardiolipin (CL) is a unique phospholipid which is present throughout the eukaryotic kingdom and is localized in mitochondrial membranes
We propose that CL is required for maintaining the mitochondrial membrane potential and that reduced membrane potential in the absence of CL leads to defects in protein import and other mitochondrial functions
The crd1⌬ Mutant Has Aberrant Composition of Acidic Phospholipids in Its Mitochondrial Membranes—Previous results indicating that the crd1⌬ mutant lacked CL were based on TLC analysis of mitochondrial membrane phospholipids [22,23,24]
Summary
MAT␣, ura, lys801, ade101, trp1-⌬1, his3-⌬200, leu2-⌬1 same as FGY3, but crd1::URA3 MAT a ade1[0] MAT a ade, oxi. Fied the S. cerevisiae structural gene encoding CL synthase (CRD1, originally named CLS1) and showed that disruption of the CRD1 gene eliminates CL from mitochondrial membranes [22]. These findings were confirmed by Tuller et al [23] and Chang et al [24]. Expression of CRD1 is highly regulated by factors affecting mitochondrial development, including carbon source, growth stage, and the presence of a mitochondrial genome [25]. These results point to the involvement of CL in critical cellular functions. We investigated the role of CL in mitochondrial function by characterizing the physiological effects of eliminating CL from the membrane
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