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

The Saccharomyces cerevisiae gene ABC1 is required for the correct functioning of the bc1 complex of the mitochondrial respiratory chain. By functional complementation of a S. cerevisiae abc1(-) mutant, we have cloned a Schizosaccharomyces pombe cDNA, whose predicted product is 50% identical to the Abc1 protein. Significant homology is also observed with bacterial, nematode, and even human amino acid sequences of unknown function, suggesting that the Abc1 protein is conserved through evolution. The cloned cDNA corresponds to a single S. pombe gene abc1Sp, located on chromosome II, expression of which is not regulated by the carbon source. Inactivation of the abc1Sp gene by homologous gene replacement causes a respiratory deficiency which is efficiently rescued by the expression of the S. cerevisiae ABC1 gene. The inactivated strain shows a drastic decrease in the bc1 complex activity. a decrease in cytochrome aa3 and a slow growth phenotype. To our knowledge, this is the first example of the inactivation of a respiratory gene in S. pombe. Our results highlight the fact that S. pombe growth is highly dependent upon respiration, and that S. pombe could represent a valuable model for studying nucleo-mitochondrial interactions in higher eukaryotes.
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PMID:Cloning by functional complementation, and inactivation, of the Schizosaccharomyces pombe homologue of the Saccharomyces cerevisiae gene ABC1. 866 31

The nuclear ABC1 gene was isolated as a multicopy suppressor of a cytochrome b mRNA translation defect. Its inactivation leads to a respiratory deficiency suggesting a block in the bc1 segment of the respiratory chain [Bousquet, I., Dujardin, G. & Slonimski, P. P. (1991) EMBO J. 10, 2023-2031]. In the present study, we established that deleting the ABC1 chromosomal gene from Saccharomyces cerevisiae does not prevent the assembly of the bc1 complex (complex III) but markedly impairs the kinetics of its high-potential electron transfer pathway occurring on the positive, outer, side of the membrane, which results in reduced activity of the bc1 complex. In addition, the activity of complex II and its cytochrome b560 decrease drastically and complex IV activity is halved. It is also observed that the binding of the quinol to the bc1 complex ubiquinol oxidation site is affected and that adding exogenous quinones partially compensates for the respiratory deficiency in vitro, although the quinone content of mutant and wild-type mitochondria are similar. Lastly, complexes II, III and IV are found to be thermosensitive and the bc1 complex exhibits greater sensitivity than the wild-type strain to center N and P inhibitors, suggesting that the three multisubunit complexes have undergone structural modifications. The data suggest that the ABC1 gene product acts as a chaperone-like protein essential for the proper conformation and efficient functioning of the bc1 complex and the effects of the Abc1 protein on the complexes II and IV might result from interactions with the modified bc1 complex.
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PMID:The nuclear ABC1 gene is essential for the correct conformation and functioning of the cytochrome bc1 complex and the neighbouring complexes II and IV in the mitochondrial respiratory chain. 921 Apr 71