Ion transport by heart mitochondria: XXIII. The effects of lead on mitochondrial reactions

Abstract The interaction of lead with isolated beef heart mitochondria and submitochondrial particles has been investigated. The amount of lead bound by the membrane, and consequently the effects of lead on a number of mitochondrial parameters, depends on the anionic composition of the suspending medium. Up to about 140 nmoles of lead per milligram of protein can be bound passively in the absence of phosphate. The binding of increasing amounts of lead alters the passive permeability of the mitochondrial membrane to cations and to anions differentially. Lead has been shown to activate the energy-linked uptake of ions by the mitochondrion, and lead itself is accumulated by an energy-dependent reaction under a variety of conditions. The energy-dependent uptake of lead shares many of the features of the Ca 2+ accumulation reaction. The effects of lead on mitochondrial respiration appear to result from an interplay between, (a) the intrinsic susceptibility of certain enzyme systems, such as succinic dehydrogenase, to inhibition by the heavy metal, (b) activation of energy-dependent ion movements by lead and the resulting increased respiration which supports these movements, (c) energy-dependent movements of lead itself, and (d) effects of lead on substrate uptake and retention.