Mechanisms responsible for carbon tetrachloride-induced perturbation of mitochondrial calcium homeostasis

Incubation of isolated hepatocytes with CCl₄ results in early reduction of the intracellular calcium content, mostly due to loss from the mitochondrial compartment. CCl₄ treatment directly affects mitochondrial functions as indicated by the inhibition of Ca²⁺ uptake in cells permeabilized to the ion by digitonin exposure and by the reduction of intracellular ATP content in hepatocytes incubated in a glucose-free medium. Such mitochondrial damage is not caused by CCl₄-induced stimulation of lipid peroxidation since it is not prevented by α-tocopherol, used at a concentration able to inhibit completely peroxidative reactions without interfering with CCl₄ activation. All data together are in favour of a direct action of CCl₄-reactive metabolites on liver cell calcium homeostasis.