Is Zn²⁺ transported by the mitochondrial calcium uniporter?

Abstract

Zinc ions were found to inhibit Ca2' uptake by rat liver mitochondria driven by succinate respiration but not that by a valinomycin-induced membrane potential. Zn'+ at 1 PM or higher concentrations induced a lowering of the membrane potential under the former but not the latter conditions. It is concluded that it is the lowered membrane potential in the presence of Zn" that reduces the rate of respiration-driven Car'. Ruthenium red was found to inhibit the uptake of Zn2+ but had no influence on its action upon the membrane potential. Zn2' did not affect the Ruthenium red-insensitive Ca'+ et&ix. Ca" stimulated the uptake of Zn 2+ . It is concluded that Zn" may be transported by the mitochondrial calcium uniporter but that it may have access to sites required for inhibition of respiration by other routes.

Zinc Is a Potent Inhibitor of Thiol Oxidoreductase Activity and Stimulates Reactive Oxygen Species Production by Lipoamide Dehydrogenase

“…Internalization of cytosolic Zn 2ϩ into the mitochondrial matrix has not been unequivocally demonstrated. However, indirect evidence was pro- Zn 2ϩ Stimulates ROS Production by LADH (30). Zn 2ϩ inhibition of respiration in isolated, intact mitochondria in a substrate-dependent manner (10) provides further indirect evidence of Zn 2ϩ internalization by mitochondria.…”

Zn2+ Inhibits α-Ketoglutarate-stimulated Mitochondrial Respiration and the Isolated α-Ketoglutarate Dehydrogenase Complex

“…Zn 2ϩ has been implicated in several mitochondrial changes, such as ion transport (55)(56)(57) and membrane swelling (33,56,58,59). Membrane swelling has been associated with the opening of the mitochondrial permeability transition pore, loss of membrane potential, and uncoupling of respiration (60).…”

Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer

“…' Brierly and Knight (1967) reported that heart mitochondria accumulated zinc by energy-dependent and by passive processes depending upon the conditions employed; but free Zn + + ions in the range of 100-500 μM was employed in those studies. It has been suggested that free Zn + + ions enter the mitochondria via the calcium uniporter (Saris and Niva, 1994). However those studies were also conducted with unphysiological concentrations of free Zn + + ions.…”