title: Zinc toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes.
abstract: Although zinc (Zn) is a known environmental toxicant, its impact on the cellular energy-producing machinery is not well established. This study investigated the influence of this divalent metal on the oxidative ATP producing network in human hepatocellular carcinoma (HepG2) cells. Zn-challenged cells contained more oxidized proteins and lipids compared with control cells. Zn severely impeded mitochondrial functions by inhibiting aconitase, alpha-ketoglutarate dehydrogenase, isocitrate dehydrogenase-NAD+ dependent, succinate dehydrogenase and cytochrome C oxidase Zn-exposed cells had a disparate mitochondrial metabolism compared with the control cells and produced significantly less ATP. However, the expression of isocitrate dehydrogenase-NADP+ dependent was more prominent in cells treated with Zn. Hence, Zn-induced pathologies may be due to the inability of the mitochondria to generate energy effectively.
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E 2C6, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lemire
authors.forename: Ryan
authors.initials: R
authors.lastname: Mailloux
authors.forename: Vasu D
authors.initials: VD
authors.lastname: Appanna
mesh_terms: D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D045744:Cell Line, Tumor; D002712:Chlorides / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D002712:Chlorides; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D011506:Proteins; D017967:Zinc Compounds; C016837:zinc chloride; D000255:Adenosine Triphosphate; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D000154:Aconitate Hydratase