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 alpha-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.