Genetics of Yeast Coenzyme QH2-Cytochrome C Reductase

Crivellone, M D; Gampel, Alexandra; Muroff, Ivor; Wu, Min; Tzagoloff, Alexander

doi:10.1007/978-1-4613-1941-2_8

Cited by 18 publications

(23 citation statements)

References 25 publications

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“…6C). The absence of the bc 1 complex in the cor1-null mutant is predicted because the Cor1 polypeptide, an extramembranous subunit that is attached to the transmembrane domains (48), is required for assembly of the bc 1 complex, and without it many of the bc 1 complex polypeptides are unstable (52,53). The effect of the coq3-null mutation on Rip1 high molecular mass complex suggests that the bc 1 complex is also dysfunctional in the absence of Coq3p.…”

Section: Coq3p and O-methyltransferase Activity Coelute With Coq4p Anmentioning

confidence: 99%

Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q

Marbois¹,

Gin²,

Faull

et al. 2005

Journal of Biological Chemistry

120

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Coenzyme Q (Q) is a redox active lipid essential for aerobic respiration in eukaryotes. In Saccharomyces cerevisiae at least eight mitochondrial polypeptides, designated Coq1-Coq8, are required for Q biosynthesis. Here we present physical evidence for a coenzyme Qbiosynthetic polypeptide complex in isolated mitochondria. Separation of digitonin-solubilized mitochondrial extracts in one-and two-dimensional Blue Native PAGE analyses shows that Coq3 and Coq4 polypeptides comigrate as high molecular mass complexes. Similarly, gel filtration chromatography shows that Coq1p, Coq3p, Coq4p, Coq5p, and Coq6p elute in fractions higher than expected for their respective subunit molecular masses. Coq3p, Coq4p, and Coq6p coelute with an apparent molecular mass exceeding 700 kDa. Coq3 O-methyltransferase activity, a surrogate for Q biosynthesis and complex activity, also elutes at this high molecular mass. We have determined the quinone content in lipid extracts of gel filtration fractions by liquid chromatography-tandem mass spectrometry and find that demethoxy-Q 6 is enriched in fractions with Coq3p. Co-precipitation of biotinylated-Coq3 and Coq4 polypeptide from digitoninsolubilized mitochondrial extracts shows their physical association. This study identifies Coq3p and Coq4p as defining members of a Q-biosynthetic Coq polypeptide complex. Coenzyme Q (ubiquinone or Q) 1 is a redox active lipid containing a long polyprenyl tail attached to a fully substituted benzoquinone ring. The number (n) of isoprene units in the polyprenyl tail (Q n ) is distinct in different organisms; humans produce Q 10 , Caenorhabditis elegans Q 9 , Escherichia coli Q 8 , and Saccharomyces cerevisiae Q 6 . Within the inner mitochondrial membrane Q functions in respiratory electron transport, where it transfers two electrons from either complex I or complex II to complex III (1). Q is present in almost all organisms, with the quantity roughly matching the respiratory capability of the tissue from which it is isolated (2). In addition to this role, Q has been found to act as a chain-breaking antioxidant (3) and to be involved in the electron transport chains of plasma and lysosomal membranes (4, 5). Q supplementation in humans slows the functional decline in patients with Parkinson disease (6), is useful for treating patients with respiratory chain defects (7), and has promise as a treatment in other neurodegenerative diseases (8).As observed with other redox active compounds, Q has the potential to act as a source of oxidative stress. In certain species, the amount of reactive oxygen species generated by mitochondria has been related to Q content (9, 10). These described dual roles as antioxidant and prooxidant associate Q with both extended and shortened life spans. C. elegans fed E. coli diets lacking Q 8 , and C. elegans clk-1 mutants with defects in Q biosynthesis show increased life spans, and we have proposed that the decreased levels of Q are associated with a decreased level of the Q semiquinone radical (Q . ) and a decreased propensity to...

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Section: Coq3p and O-methyltransferase Activity Coelute With Coq4p Anmentioning

confidence: 99%

Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q

Marbois¹,

Gin²,

Faull

et al. 2005

Journal of Biological Chemistry

120

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“…In the first type, mutations in the 5'-untranslated leaders Possibly identical to CBP7 [94] of various transcripts lead to the accumulation of stable, but untranslatable mRNAs. The changes, which so far arc all located at some distance upstream of the initiator AUG, presumably identify sites in the mRNA that act as targets for components of the translational-initiation apparatus [56, 891.…”

Section: Translation Vnrna Sdrctionmentioning

confidence: 99%

Nucleo‐mitochondrial interactions in yeast mitochondrial biogenesis

Grivell

1989

European Journal of Biochemistry

212

100

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“…The crystal structure of complex III has been resolved (Iwata et al, 1998), providing further evidence that the peculiar feature of nine consecutive glutamic residues at the N-terminal of the Hinge protein may be the site of interaction with the basic protein cytochrome c. The protein is highly conserved from yeast to humans. In yeast, the 17 kDa subunit of complex III is the homolog of Hinge protein and deletion mutants are still capable of growth on a nonfermentable substrate, therefore implying that it is not essential for the assembly and function of complex III (Crivellone et al, 1988;Schoppink et al, 1988). Nonetheless, there is evidence that it may exert a regulatory role of complex III and of its association with cytochrome c (Kim et al, 1989;Schoppink et al, 1989).…”

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confidence: 99%

UQCRH gene encoding mitochondrial Hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines

et al. 2003

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We previously reported the identification of a novel zincfinger gene, designated ZSG, fused to Ewing sarcoma gene (EWS) by a submicroscopic paracentric inversion of 22q12 in a small round cell sarcoma presenting a translocation t(1;22)(p34;q12). We report here the molecular cloning and characterization of the breakpoint in 1p34, which encompasses the gene coding for mitochondrial Hinge protein ubiquinol-cytochrome C reductase hinge gene (UQCRH). All the three breakpoints, two on 22q12 and one in 1p34, interrupt different genes: EWS, ZSG and UQCRH. We determined the genomic structure of UQCRH, characterized its splicing variants and identified a transcribed processed pseudogene. The analysis of UQCRH expression in normal tissues and cancer cell lines revealed absent expression of UQCRH in two ovarian and one breast cancer cell lines and reduced expression in a further breast carcinoma cell line. CpG island methylation upstream exon 1 was detected in all the three cell lines with absent expression. Moreover, treatment with demethylating agent 5-azacytidine restored UQCRH expression in OAW42 ovarian cancer cells. These data provide preliminary evidence of the inactivation of UQCRH gene in cancer either by structural rearrangements or epigenetic mechanisms. Oncogene ( Keywords: EWS; sarcoma; ovarian carcinoma; hinge protein; mitochondrial complex III Sarcomas are a heterogeneous group of malignancies of mesenchymal origin that frequently display nonrandom chromosomal translations creating specific fusion genes. The Ewing family of tumors (EFT) comprises small round cell sarcomas showing moderate neural differentiation that were considered in the past as distinct entities: Ewing's sarcoma, primitive neuroectodermal tumors, peripheral neuroepithelioma and Askin tumor. It is now well documented that almost 95% of EFT share the presence of EWS-FLI1 fusion gene, detected cytogenetically as t(11;22)(q24;q12), or of four other alternative Ewing sarcoma gene (EWS) fusions with different partners (namely ERG, ETV1, FEV. E1AF) (Kovar, 1998). Other sarcoma types display specific fusion genes involving EWS and different partners: CHOP (12q13) in myxoid liposarcoma, WT1 (11p13) in intra-abdominal desmoplastic small round cell tumor, CHN/TEC (9q22) in myxoid chondrosarcoma, ATF1 (12q13) in malignant melanoma of soft parts and ZSG/ PATZ (22q12) in a small round cell sarcoma. In all cases, the identification of the translocation by FISH and/or of the fusion transcript by RT-PCR currently offers an invaluable clue for the correct diagnosis. The exact functions of EWS protein, an RNA-binding protein, are still unclear, but it is widely proven by in vitro studies that the EWS-related fusion genes act as dominant oncogenes with aberrant transcription and possibly splicing features (Arvand and Denny, 2001).We previously reported the identification of a novel fusion gene between EWS and the novel putative transcription factor ZSG, generated by an intrachromosomal rearrangement of chromosome 22, an inversion of 22q12, in a small round cel...

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Genetics of Yeast Coenzyme QH2-Cytochrome C Reductase

Cited by 18 publications

References 25 publications

Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q

Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q

Nucleo‐mitochondrial interactions in yeast mitochondrial biogenesis

UQCRH gene encoding mitochondrial Hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines

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