Disease relevance of UQCRFS1

• CONCLUSIONS: These results suggest that the UQCRFS1 gene appears to be involved in development of more aggressive phenotype of breast cancer [1].
• Unexpectedly, 3 of 22 (13.6%) touch preparations, 1 of 14 (7.1%) paraffin samples, one cell line, and the ascites sample had amplification of the UQCRFS1 region [2].
• CA125 and UQCRFS1 FISH studies of ovarian carcinoma [2].
• These BACs have been mapped to 19q12-19q13.1 and 19q11-19q13.1, respectively, and are predicted to contain the markers D19S409 and D19S919 and the gene for ubiquinol-cytochrome C reductase, Rieske iron-sulfur polypeptide1 (UQCRFS1). dmin originating from chromosome 19 have not been reported previously in hematologic malignancies [3].
• Chromatophore membranes isolated from the bacteriochlorophyll b-containing, photosynthetic purple nonsulfur bacterium, Rhodopseudomonas viridis, have been shown to contain a Rieske iron-sulfur protein, a cytochrome similar to cytochrome c1, and also at least one b-type cytochrome [4].

High impact information on UQCRFS1

• Three of the membrane-spanning polypeptides of the chloroplast cytochrome (cyt) b6f complex were sequentially released from the thylakoid membrane, in the order cyt b6, suIV and Rieske iron-sulfur protein, as the pH was increased from 10 to 12, a protocol usually employed to remove peripheral proteins from membranes [5].
• Instead, when the RISP that was attached to thylakoid membranes was first illuminated on ice, degradation proceeded in either light or darkness at equal rates suggesting a light-induced conformational change making the protein prone to degradation [6].
• The iron atoms in the Rieske iron-sulfur cluster are coordinated to the protein by two histidine nitrogens and two cysteine sulfurs [7].
• The time course of electron transfer in vitro between soluble domains of the Rieske iron-sulfur protein (ISP) and cytochrome f subunits of the cytochrome b(6)f complex of oxygenic photosynthesis was measured by stopped-flow mixing [8].
• In vitro import of the Rieske iron-sulfur protein by trypanosome mitochondria [9].

Chemical compound and disease context of UQCRFS1

• Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples [1].

Biological context of UQCRFS1

• Mapping by hybridization to a panel of monochromosomal hybrid cell lines indicated that a UQCRFS1 partial cDNA was derived from either chromosome 19 or 22 [10].
• The UQCRFS1 protein is also known as complex III of the mitochondrial respiratory chain [2].
• The purpose of this study is to evaluate the significance of the ubiquinol cytochrome c reductase UQCRFS1 gene amplification in primary breast cancers [1].
• Assignment of the gene (UQCRFS1) for the Rieske iron-sulfur protein subunit of the mitochondrial cytochrome bc1 complex to the 22q13 and 19q12-q13.1 regions of the human genome [11].
• Import of the Rieske iron-sulfur protein subunit of the cytochrome c reductase complex requires a membrane potential, ATP, and a protein component on the mitochondrial surface [9].

Anatomical context of UQCRFS1

• RESULTS: We report the identification of a modified variant of the Rieske iron-sulfur protein, a component of the mitochondrial cytochrome bc1 complex, whose isoelectric point is shifted toward more alkaline values in the hippocampus of kindled rats [12].
• 2D gel electrophoresis by blue-native-PAGE and SDS-PAGE showed that RISP existed as an apparent monomer in mitochondrial membranes in addition to forming a complex with ubiquinol-cytochrome c reductase [13].
• Exogenous reactive oxygen species increased the plasma membrane Na,K-ATPase degradation, whereas, in mitochondrial DNA deficient rho(0) cells and in cells transfected with small interfering RNA against Rieske iron sulfur protein, the hypoxia-mediated Na,K-ATPase degradation was prevented [14].

Associations of UQCRFS1 with chemical compounds

• Physicochemical aspects of the movement of the rieske iron sulfur protein during quinol oxidation by the bc(1) complex from mitochondria and photosynthetic bacteria [15].
• Based on the atomic structures of the mitochondrial cytochrome bc(1) complex, it has been proposed that the soluble domain of the [2Fe-2S] Rieske iron-sulfur protein (ISP) must rotate by ca. 60 degrees and translate through an appreciable distance between two binding sites, proximal to cytochrome c(1) and to the lumen-side quinol binding site [16].
• Several quinone inhibitors, all of which contain a halogen substituent and a bulky alkyl side chain, cause a shift in the EPR signal of the reduced Rieske iron-sulfur center from g = 1.90 to g = 1.94 [17].
• Interaction of stigmatellin and DNP-INT with the Rieske iron-sulfur center of the chloroplast cytochrome b6-f complex [18].
• In coenzyme Q-cycles, it is proposed that one electron from the quinol reduces the Rieske iron sulfur center (Em approximately 280 mV) and the remaining electron on the semiquinone reduces cytochrome br (Em approximately -60 mV) [19].

Physical interactions of UQCRFS1

• Here we show that a small interfering RNA (siRNA) against the Rieske iron-sulfur protein of mitochondrial complex III prevents the hypoxic stabilization of HIF-1 alpha protein [20].

Other interactions of UQCRFS1

• Using RNAi to suppress expression of the Rieske iron-sulfur protein of complex III, hypoxia-induced HIF-1 alpha stabilization is attenuated, and ROS production, measured using a novel ROS-sensitive FRET probe, is decreased [21].
• The reducing equivalents accepted and donated by the portion of the respiratory chain with half-reduction potentials greater than 200 mV are equal to those required for the known components (cytochrome a3 and the high-potential copper plus cytochrome a, 'visible copper', cytochrome c1, cytochrome c, and the Rieske iron-sulfur protein) [22].
• Irrespectively, whether the fluidity of membrane lipids was elevated or decreased electron flow rates to the Rieske iron sulfur protein and to low potential cytochrome b were drastically reduced [23].

Analytical, diagnostic and therapeutic context of UQCRFS1

• To examine UQCRFS1 gene amplification, we employed fluorescent in situ hybridization using BACs RP11-46I12 that harbors UQCRFS1 gene, RP11-110J19 that overlaps to RP11-46I12, and CA125 as a control gene [1].
• CYC1 and RISP have lower levels of sequence divergence between populations than CYTB, but, again, sequence analysis gives no evidence for positive selection acting on them [24].
• We have designed generic PCR primers targeting the gene fragment encoding the Rieske iron sulfur center common to all PAH dioxygenase enzymes [25].
• A binary subcomplex consisting of cytochrome f and the Rieske iron-sulfur protein was observed under these conditions by three different methods: (a) hydroxyapatite chromatography; (b) extraction with an isopropanol/water/trifluoroacetic acid mixture; and (c) gel filtration in the presence of low SDS concentrations [26].

References