Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We purified an NADPH-dependent coenzyme Q reductase (NADPH-CoQ reductase) in rat liver cytosol and compared its enzymatic properties with those of the other CoQ10 reductases such as NADPH: quinone acceptor oxidoreductase 1 (NQO1), lipoamide dehydrogenase, thioredoxine reductase and glutathione reductase. NADPH-CoQ reductase was the only enzyme that preferred NADPH to NADH as an electron donor and was also different from the other CoQ10 reductases in the sensitivities to its inhibitors and stimulators. Especially, Zn2+ was the most powerful inhibitor for NADPH-CoQ reductase, but CoQ10 reduction by the other CoQ10 reductases could not be inhibited by Zn2+. Furthermore, the reduction of the CoQ9 incorporated into HeLa cells was also inhibited by Zn2+ in the presence of pyrithione, a zinc ionophore. Moreover, NQO1 gene silencing in HeLa cells by transfection of a small interfering RNA resulted in lowering of both the NQO1 protein level and the NQO1 activity by about 75%. However, this transfection did not affect the NADPH-CoQ reductase activity and the reduction of CoQ9 incorporated into the cells. These results suggest that the NADPH-CoQ reductase located in cytosol may be the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells.
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PMID:NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells. 1909 1

Mitochondrial disorders are often associated with primary or secondary CoQ10 decrease. In clinical practice, Coenzyme Q10 (CoQ10) levels are measured to diagnose deficiencies and to direct and monitor supplemental therapy. CoQ10 is reduced by complex I or II and oxidized by complex III in the mitochondrial respiratory chain. Therefore, the ratio between the reduced (ubiquinol) and oxidized (ubiquinone) CoQ10 may provide clinically significant information in patients with mitochondrial electron transport chain (ETC) defects. Here, we exploit mutants of Caenorhabditis elegans (C. elegans) with defined defects of the ETC to demonstrate an altered redox ratio in Coenzyme Q9 (CoQ9), the native quinone in these organisms. The percentage of reduced CoQ9 is decreased in complex I (gas-1) and complex II (mev-1) deficient animals, consistent with the diminished activity of these complexes that normally reduce CoQ9. As anticipated, reduced CoQ9 is increased in the complex III deficient mutant (isp-1), since the oxidase activity of the complex is severely defective. These data provide proof of principle of our hypothesis that an altered redox status of CoQ may be present in respiratory complex deficiencies. The assessment of CoQ10 redox status in patients with mitochondrial disorders may be a simple and useful tool to uncover and monitor specific respiratory complex defects.
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PMID:Altered redox status of coenzyme Q9 reflects mitochondrial electron transport chain deficiencies in Caenorhabditis elegans. 2084 80

By using "our devised up-to-the-second technique" over 30 years ago, we succeeded in the first isolation in the world of the three different kinds of mammalian cell mutants defective in the biosynthesis on each of phosphatidylserine (PS), cardiolipin (CL) and sphingomyelin (SM) from the parental CHO cells. As the results, we found that during the biosyntheses of PS and SM, the biosynthetic precursor or the final lipids are transported from their synthesized intracellular organelles to the plasma membranes via the other intracellular organelles. We further clarified the presence of the reversed routes for PS and SM from the plasma membranes to their synthesized organelles too. Our first epoch-making finding is not only the cycling inter-conversion reactions between PS and PE catalyzed by PSS-II and PSD but also their simultaneous transferring between MAM and Mit (found by O. Kuge). Our second finding is "the ceramide-trafficking protein (CERT)" working as the specific transfer protein of ceramide from the ER to the Golgi apparatus, during the SM biosynthesis (by K. Hanada). As for their new biological roles, we clarified possible contribution of PS and/or PE to the fusion process between viral envelope and endosomal membrane, releasing the genetic information of the virus to the host cytoplasm. CL is contributing to the functional NADH-ubiquinone reductase activity by keeping the right structure of Coenzyme Q9 for its functioning. SM and cholesterol form the microdomain within the plasma membrane, so-called "the raft structure" where the GPI-anchored proteins are specifically located for their functioning.
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PMID:Reminiscence of our research on membrane phospholipids in mammalian cells by using the novel technology. 2322 49

The level of coenzyme Q (CoQ) has been shown to decrease in an age-dependent manner in several types of animals. However, whether CoQ-dependent mitochondrial function decreases with aging remains unclear. In this study, we found that mitochondrial complexes I and II exhibited significantly reduced oxygen consumption in the brains of aged male mice relative to young male mice, although this decrease in oxygen consumption was not accompanied by a change in the CoQ9 or CoQ10 content. Nevertheless, the administration of exogenous CoQ10 significantly increased the content of CoQ10 and CoQ9 in the brain mitochondria of aged male mice and restored complex I- and II-mediated oxygen consumption to levels comparable to those observed in young mice. These results indicate that mitochondrial oxygen consumption in the brain decreases in aged male mice. Furthermore, these results suggest that exogenous CoQ10 restores mitochondrial oxygen use to levels equivalent to those observed in young mice.
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PMID:Exogenous administration of coenzyme Q10 restores mitochondrial oxygen consumption in the aged mouse brain. 2433 74