Ion Transport in Mitochondria

(1) Isolated mitochondria are able to take up potassium from relatively low external K+ concentrations. The uptake is energy-dependent and may be shown to take place against a concentration gradient. (2) It is not certain whether this K+ uptake is a true “active” transport since relevant data on membrane potential are lacking. It is reasonable to infer, however, that the K+ uptake is at least in part due to an active process. (3) K+ uptake can take place in one of two modes: either in exchange for H+, or in association with a penetrating anion. Various studies indicate that penetrating anions are acetate, phosphate, and possibly substrate anions. Chloride, sulfate, and nitrate do not appear to penetrate with any ease (at least into rat-liver mitochondria). (4) The methods for studying K+ uptake greatly influence the results. When cation uptake is assessed by separation of the particles from the system followed by flame photometric analysis, relatively low rates of K+ uptake and small total uptakes are observed. The use of cationsensitive electrodes, on the other hand, reveals much more rapid and extensive K+ uptake than previously found. (5) Inhibitor studies reveal that when respiration is blocked K+ uptake is prevented in the absence of added ATP. Oligomycin blocks K+ uptake only when added ATP is the energy source and has no effect on uptake energized by substrate oxidation. It is concluded that some intermediate step in ATP synthesis can be used as an energy source for cation transfer. Valinomycin, a toxic antibiotic, has a specific property of stimulating K+ uptake by mitochondria. This uptake is associated both with H+ exchange and uptake of penetrating anion when available. Rates are greater in the latter condition. (6) Divalent cations such as Mg2+, Mn2+, Ca2+, and Sr2+ are taken up by an apparently energy-linked process. The doubts expressed about the inactive nature of K+ uptake apply even more forcibly to the transfer of divalent cations since they may be sequestered as un-ionized compounds within the particles. Such un-ionized materials form sinks for divalent cations. It is not possible to state even that uptakes of divalent cations take place against concentration gradients because the internal concentrations cannot be calculated. (7) The relationship between mitochondrial cation transport and transport in whole cells is hard to assess at the present time; information is inadequate. Certain obvious dissimilarities come to mind; in general, the parent tissues conduct Na+ for K+ exchanges, do not exhibit H+ for K+ exchanges, and do not take up K+ salts. Sensitivity to cardiac glycosides has not been tested adequately in mitochondrial systems. In the case of rat-liver mitochondria, however, both centrifugal and electrode methods show that K+ uptake can be blocked by strophanthin-G and that the inhibition can be reversed by increasing external K+ concentration. (8) The role of specific molecules in the transport of cations by mitochondria has scarcely been studied. The possibility that phosphorylated intermediates of oxidative phosphorylation may energize mitochondrial cation transport has only recently been considered and few studies have appeared.