Advance Access publication February 17, 2012 Differential Inhibition of Electron Transport Chain Enzyme Complexes by Cadmium and Calcium in Isolated Rainbow Trout (Oncorhynchus mykiss)

Impairment of the electron transport chain (ETC) is implicated in cadmium (Cd)- and calcium (Ca)-induced mitochondrial dysfunction. To localize the sites of the impairment, effects of 0–50mM Cd and Ca, singly and in combination, on complex I- to IV-driven respirations were investigated using isolated rainbow trout liver mitochondria. Mitochondrial Cd/Ca accumulation and respiration rates were measured following sequential inhibition and activation of complexes I, II, III, and IV. Mitochondrial adenosine triphosphate (ATP) synthesis was measured on exposure to (micromolar) 20 Cd and 50 Ca, singly and combined, whereas malondialdehyde (MDA) was measured on incubation with 0–1mM Cd and/or Ca. We show that mitochondrial accumulation of Cd and Ca and the states 3 and 4 rates of respiration depended on the active ETC complex. Although complex IV was highly recalcitrant to Cd and/or Ca, dose-dependent inhibitions of complex I-, II-, an