title: Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10)  in human cells.
abstract: Little is known about the regulation of endogenous CoQ(10) levels in response to mitochondrial dysfunction or oxidative stress although exogenous CoQ(10) has been extensively used in humans. In this study, we first demonstrated that acute treatment of antimycin A, an inhibitor of mitochondrial complex III, and the absence of mitochondrial DNA suppressed CoQ(10) levels in human 143B cells. Because these two conditions also enhanced formation of reactive oxygen species (ROS), we further investigated whether oxidative stress or mitochondrial dysfunction primarily contributed to the decrease of CoQ(10) levels. Results showed that H(2)O(2) augmented CoQ(10) levels, but carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a chemical uncoupler, decreased CoQ(10) levels in 143B cells. However, H(2)O(2) and FCCP both increased mRNA levels of multiple COQ genes for biosynthesis of CoQ(10) . Our findings suggest that ROS induced CoQ(10) biosynthesis, whereas mitochondrial energy deficiency caused secondary suppression of CoQ(10) levels possibly due to impaired import of COQ proteins into mitochondria.
authors.affiliation: Department and Graduate Institute of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, Republic of China. yen@mail.cgu.edu.tw
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Yen
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Chen
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Chen
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D061209:Proton Ionophores / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial; D061209:Proton Ionophores; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000968:Antimycin A; D006861:Hydrogen Peroxide; D014450:Electron Transport Complex III; C024989:coenzyme Q10