Role of Calcium and Mitochondria in MeHg-Mediated Cytotoxicity

Methylmercury (MeHg) mediated cytotoxicity is associated with loss of intracellular calcium (Ca(2+)) homeostasis. The imbalance in Ca(2+) physiology is believed to be associated with dysregulation of Ca(2+) intracellular stores and/or increased permeability of the biomembranes to this ion. In this paper we summarize the contribution of glutamate dyshomeostasis in intracellular Ca(2+) overload and highlight the mitochondrial dysfunctions induced by MeHg via Ca(2+) overload. Mitochondrial disturbances elicited by Ca(2+) may involve several molecular events (i.e., alterations in the activity of the mitochondrial electron transport chain complexes, mitochondrial proton gradient dissipation, mitochondrial permeability transition pore (MPTP) opening, thiol depletion, failure of energy metabolism, reactive oxygen species overproduction) that could culminate in cell death. Here we will focus on the role of oxidative stress in these phenomena. Additionally, possible antioxidant therapies that could be effective in the treatment of MeHg intoxication are briefly discussed.