Cd2+ -promoted mitochondrial permeability transition: a comparison with other heavy metals.

We compared action of Cd(2+), Hg(2+), and Cu(2+) on isolated rat liver mitochondria in the absence of added Ca(2+) and P(i). The heavy-metal ions produced dose-dependently: (1) enhanced membrane permeabilization manifested in mitochondrial swelling and activation of basal respiration, (2) inhibition of uncoupler-stimulated respiration, and (3) membrane potential dissipation. Among the metals, Cu(2+) exhibited maximal stimulatory effect on basal respiration and minimal inhibitory action on DNP-uncoupled respiration whilst Cd(2+) promoted the strongest depression of uncoupled respiration and the largest swelling in NH(4)NO(3) medium. Dithiothreitol induced a basal respiration release if added after high [Cd(2+)] and [Hg(2+)], and the stimulation was CsA-insensitive.