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

We compared action of Cd2+, Hg2+, and Cu2+ on isolated rat liver mitochondria in the absence of added Ca2+ and Pi. The heavy-metal ions produced dose-dependently: (1) enhanced membrane permeabilizaton manifested in mitochondrial swelling and activation of basal respiration, (2) inhibition of uncoupler-stimulated respiration, and (3) membrane potential dissipation. Among the metals, Cu2+ exhibited maximal stimulatory effect on basal respiration and minimal inhibitory action on DNP-uncoupled respiration whilst Cd2+ promoted the strongest depression of uncoupled respiration and the largest swelling in NH4NO3 medium. Dithiothreitol induced a basal respiration release if added after high [Cd2+] and [Hg2+], and the stimulation was CsA-insensitive.