Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency

Yen, Hsiu-Chuan; Liu, Yichun; Kan, C.-C.; Wei, Hsing-Ju; Lee, Szu-Hsien; Wei, Yau‐Huei; Feng, Yu-Hsiu; Chen, Chih‐Wei; Huang, Chin‐Chang

doi:10.1016/j.bbagen.2016.05.005

Cited by 19 publications

(19 citation statements)

References 44 publications

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“…We have demonstrated that modest reduction in CoQ 10 levels were present in peripheral blood leukocytes of affected patients while in skeletal muscles CoQ 10 levels were much more reduced. The overall effect on CoQ 10 levels, especially in skeletal muscle tissue, are consistent with the importance of COQ5 in ubiquinone synthesis (Chen, Liu, & Yen, 2013;Yen et al, 2016), and confirm the finding that destabilization of the COQ5containing protein complex in human cells reduces CoQ 10 levels (Yen et al, 2016). It is important to note, however, that although the CoQ 10 levels low, there is still some amount of CoQ 10 produced in leukocytes and muscle.…”

Section: Discussionsupporting

confidence: 83%

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

et al. 2017

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Section: Discussionsupporting

confidence: 83%

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

et al. 2017

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“…Numerous complex Q interactions were also confirmed by cell-free protein expression and purification studies [117], and by immunoprecipitation-immunoblot studies of COQ5 [77], COQ8A [87], and COQ8B [118]. Additionally, native gel electrophoresis studies tracking COQ5 suggested the presence of a high molecular weight complex Q in human cells [102]. Select lipids and small molecules have also been shown to bind to individual complex Q proteins, such as COQ9 and COQ8A [87, 116], suggesting that mammalian complex Q contains nonproteinacious components.…”

Section: The Coq Biosynthetic Complexmentioning

confidence: 96%

“…The C2 -methylation is catalyzed by COQ5 in eukaryotes [75–77, 102] and UbiE in prokaryotes [103, 104]. Lysates containing Coq5p or UbiE can catalyze demethoxy-demethyl-CoQ (DDMQ) C 2-methylation in vitro in a reaction that depends on SAM and NADH [75].…”

Section: The Terminal Stage Of Coq Biosynthesis – Head Group Modificamentioning

confidence: 99%

Biochemistry of Mitochondrial Coenzyme Q Biosynthesis

Stefely

Pagliarini

2017

Trends in Biochemical Sciences

273

290

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Coenzyme Q (CoQ, ubiquinone) is a redox active lipid produced across all domains of life that functions in electron transport and oxidative phosphorylation and whose deficiency causes human diseases. Yet, CoQ biosynthesis has not been fully defined in any organism. Several proteins with unclear molecular functions facilitate CoQ biosynthesis through unknown means, and multiple steps in the pathway are catalyzed by currently unidentified enzymes. Here we highlight recent progress toward filling these knowledge gaps through both traditional biochemistry and cutting-edge “omics” approaches. To help fill the remaining gaps, we present questions framed by the recently discovered CoQ biosynthetic complex and by putative biophysical barriers. Mapping CoQ biosynthesis, metabolism, and transport pathways has great potential to enhance treatment of numerous human diseases.

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“…It is possible that Cr(VI) induced ETFDH inhibition, causing mitochondrial dysfunction to disturb the expression of genes in CoQ10 biosynthesis. This is supported by Hsiu-Chuan’s study, which reported the suppressive effect of FCCP on COQ5 levels in association with decreased mitochondrial membrane potential, mitochondrial ATP production, and CoQ10 levels [33]. Interestingly, ADCK3 was upregulated after exposure to Cr(VI), although not significantly.…”

Section: Discussionmentioning

confidence: 63%

CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity

Zhong

Sá

et al. 2017

IJMS

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To investigate the toxic mechanism of hexavalent chromium Cr(VI) and search for an antidote for Cr(VI)-induced cytotoxicity, a study of mitochondrial dysfunction induced by Cr(VI) and cell survival by recovering mitochondrial function was performed. In the present study, we found that the gene expression of electron transfer flavoprotein dehydrogenase (ETFDH) was strongly downregulated by Cr(VI) exposure. The levels of coenzyme 10 (CoQ10) and mitochondrial biogenesis presented by mitochondrial mass and mitochondrial DNA copy number were also significantly reduced after Cr(VI) exposure. The subsequent, Cr(VI)-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species (ROS) accumulation, caspase-3 and caspase-9 activation, decreased superoxide dismutase (SOD) and ATP production, increased methane dicarboxylic aldehyde (MDA) content, mitochondrial membrane depolarization and mitochondrial permeability transition pore (MPTP) opening, increased Ca2+ levels, Cyt c release, decreased Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI)-induced deleterious changes were attenuated by pretreatment with CoQ10 in L-02 hepatocytes. These data suggest that Cr(VI) induces CoQ10 deficiency in L-02 hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial dysfunction in Cr(VI) poisoning and that exogenous administration of CoQ10 may restore mitochondrial function and protect the liver from Cr(VI) exposure.

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Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency

Cited by 19 publications

References 44 publications

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

Biochemistry of Mitochondrial Coenzyme Q Biosynthesis

CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity

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