Role of mitochondrial calcium in hypochlorite induced oxidative damage of cells

Cheshchevik, V.T. ✉; Krylova, N.G.; Сheshchevik, N.G.; Lapshina, E.A.; Semenkova, G.N.; Zavodnik, I.B.

English Scientific Article (Journal Article)
Published: BIOCHIMIE 0300-9084 1638-6183 184 pp. 104-115 2021
  • SJR Scopus - Biochemistry: Q1
Hypochlorite (HOCl) is one of the most important mediators of inflammatory processes. Recent evidence demonstrates that changes in intracellular calcium pool play a significant role in the damaging effects of hypochlorite and other oxidants. Mitochondria are shown to be one of the intracellular targets of hypochlorite. But little is known about the mitochondrial calcium pool changes in HOCl-induced mitochondrial dysfunction. Using isolated rat liver mitochondria, we showed the oxidative damage of mitochondria (GSH oxidation and mixed protein-glutathione formation without membrane lipid peroxidation) and alterations in the mitochondrial functional parameters (decrease of respiratory activity and efficiency of oxidative phosphorylation, NADH and FADH coenzyme levels, and membrane potential) under hypochlorite action (50–300 μM). Simultaneously, the mitochondrial calcium release and swelling were demonstrated. In the presence of EGTA, the damaging effects of HOCl were less pronounced, reflecting direct involvement of mitochondrial Ca2+ in mechanisms of oxidant-induced injury. Furthermore, exposure of HeLa cells to hypochlorite resulted in a considerable increase in cytoplasmic calcium concentrations and a decrease in mitochondrial ones. Applying specific inhibitors of calcium transfer systems, we demonstrated that mitochondria play a key role in the redistribution of cytoplasmic Ca2+ ions under hypochlorite action and act as mediators of calcium release from the endoplasmic reticulum into the cytoplasm. © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
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2021-12-06 08:57