Inhibition by aluminum hydroxide of the voltage-dependent closure of the mitochondrial channel, VDAC.

Micromolar quantities of aluminum have been found (Dill et al. (1987) J. Membrane Biol. 99, 187-196) to reduce the voltage dependence of the mitochondrial outer membrane channel, VDAC, from Neurospora crassa. In the present study, various metallic and organic ions were tested for possible aluminum-like effect, and only the trivalent metals exhibited a similar ability to reduce the channels voltage dependence. However, trivalency alone was not sufficient because lanthanum (III) had no effect. Quantitative analyses with three group IIIA metals (A1, Ga, and In) showed that, of the structural characteristics examined, the ability to form sufficient M(OH)3 at experimental pH was the primary property shared by all the effective metals. While providing new insight into the nature of VDAC's sensor, these results also indicate that aluminum-cell interaction may result from the presence of AI(OH)3 in solution in addition to the widely accepted AI3+-mediated interactions. While the [AI3+] is vanishingly low at neutral pH, the trihydroxide is the major form and should be considered as an important candidate for aluminum-induced cellular effects.