Zinc toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E 2C6, Canada.
Journal of Applied Toxicology (Impact Factor: 3.17). 03/2008; 28(2):175-82. DOI: 10.1002/jat.1263
Source: PubMed

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.

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