Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiolipin (CL) is a unique dimeric phospholipid localized primarily in the mitochondrial membrane. In eukaryotes, the enzyme CL synthase catalyses the synthesis of CL from two lipid substrates, CDP-diacylglycerol and phosphatidylglycerol. In earlier studies, we reported the purification of CL synthase from Saccharomyces cerevisiae and the cloning of the gene CRD1 (previously called CLS1) that encodes the enzyme. Because CL is an important component of the mitochondrial membrane, knowledge of its regulation will provide insight into the biogenesis of this organelle. To understand how CL synthesis is regulated, we analysed CRD1 expression by Northern blot analysis of RNA extracted from cells under a variety of growth conditions. CRD1 expression is regulated by mitochondrial development factors. CRD1 levels were 7- to 10-fold greater in stationary than in logarithmic growth phase, and threefold greater in wild-type than in rho 0 mutants. Expression was somewhat elevated during growth in glycerol/ethanol versus glucose media. In contrast, CRD1 expression was not regulated by the phospholipid precursors inositol and choline, and was not altered in the regulatory mutants ino2, ino4 and opi1. Mutations in cytochrome oxidase assembly, which led to reduced Crd1p enzyme activity, did not affect CRD1 expression. The crd1 null mutant makes a truncated CRD1 message. Although the null mutant can grow on both fermentable and non-fermentable carbon sources at lower temperatures, it cannot form colonies at 37 degrees C. In conclusion, CRD1 expression is controlled by factors affecting mitochondrial development, but not by the phospholipid precursors inositol and choline. Expression of CRD1 is essential for growth at elevated temperatures, suggesting that either CL or Crd1p is required for an essential cellular function.
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PMID:Cardiolipin synthase expression is essential for growth at elevated temperature and is regulated by factors affecting mitochondrial development. 998 37

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.
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PMID:Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function. 1077 14

Cytochrome bc(1) complex (complex III) and cytochrome c oxidase complex (complex IV) are multisubunit homodimers that are essential components of the mitochondrial respiratory chain. Complexes III and IV associate to form a supercomplex that can be displayed using blue native polyacrylamide gel electrophoresis. Both homodimeric complexes contain tightly associated cardiolipin (CL) required for function. We report here that in a crd1Delta strain of yeast (null in expression of CL synthase) approximately 90% of complexes III and IV were observed as individual homodimers; only the supercomplex was observed with CRD1 wild type cells. Introduction of a plasmid born copy of the CRD1 gene under exogenous regulation by doxycycline made possible controlled variation in the in vivo CL levels. At an intermediate level of CL, a mixture of individual homodimers (30%) and supercomplex (70%) was observed. These results strongly indicate that CL plays a central role in higher order organization of components of the respiratory chain of mitochondria.
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PMID:Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. 1236 41

In eukaryotic cells, the phospholipid cardiolipin (CL) is primarily found in the inner mitochondrial membrane. Saccharomyces cerevisiae mutants, unable to synthesize CL because of a null allele of the CRD1 gene (encodes CL synthase), have been reported with different phenotypes. Some mutants, when grown on a nonfermentable carbon source at elevated temperatures, exhibit mitochondrial DNA instability, loss of viability, and significant defects in several functions that rely on the mitochondrial energy transducing system (ETS). These mutants also lack the immediate precursor to CL, phosphatidylglycerol (PG), when grown on glucose as a carbon source. Other mutants show reduced growth efficiency on a nonfermentable carbon source but much milder phenotypes associated with growth at elevated temperatures and increased levels of PG when grown on glucose. We present evidence that mitochondrial DNA instability, loss of viability, and defects in the ETS exhibited at elevated temperatures by some mutants are caused by the reduced expression of the PET56 gene in the presence of the his3 Delta 200 allele and not the lack of CL alone. We also found that PG is present and elevated in all crd1 Delta strains when grown on glucose. A supermolecular complex between complex III and complex IV of the mitochondrial ETS detected in wild type cells was missing in all of the above crd1 Delta cells. The level of components of the ETS was also reduced in crd1 Delta cells grown at elevated temperatures because of reduced gene expression and not reduced stability. These results suggest that all phenotypes reported for cells carrying the his3 Delta 200 allele and lacking CL should be re-evaluated.
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PMID:Cardiolipin is not required to maintain mitochondrial DNA stability or cell viability for Saccharomyces cerevisiae grown at elevated temperatures. 1284 9