Role of phosphate and other proton-donating anions in respiration-coupled transport of Ca2+ by mitochondria.
Measurements of extra oxygen consumption, (45)Ca(2+) uptake, and the osmotic expansion of the matrix compartment show that not all permeant anions are capable of supporting and accompanying the energy-dependent transport of Ca(2+) from the medium into the matrix in respiring rat-liver mitochondria. Phosphate, arsenate, acetate, butyrate, beta-hydroxybutyrate, lactate, and bicarbonate + CO(2) supported Ca(2+) uptake, whereas the permeant anions, nitrate, thiocyanate, chlorate, and perchlorate, did not. The active anions share a common denominator, the potential ability to donate a proton to the mitochondrial matrix; the inactive anions lack this capacity. Phosphate and the other active permeant anions move into the matrix in response to the alkaline-inside electrochemical gradient of protons generated across the mitochondrial membrane by electron transport, thus forming a negative-inside anion gradient. It is postulated that the latter gradient is the immediate "pulling" force for the influx of Ca(2+) on the electrogenic Ca(2+) carrier in respiring mitochondria under intracellular conditions. Since mitochondria in the cell are normally exposed to an excess of phosphate (and the bicarbonate-CO(2) system), particularly in state 4, inward transport of these proton-yielding anions probably precedes and is necessary for inward transport of Ca(2+) and other cations under biological conditions. These observations indicate that a negative-inside gradient of phosphate generated by electron transport is a common step and provides the immediate motive power not only for (a) the inward transport of dicarboxylates and tricarboxylates and (b) the energy-dependent exchange of external ADP(3-) for internal ATP(4-) during oxidative phosphorylation, as has already been established, but also for (c) the inward transport of Ca(2+), K(+), and other cations.
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D000838:Anions; D001151:Arsenic / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002704:Chlorates / Q000494:pharmacology; D004579:Electron Transport; D006885:Hydroxybutyrates / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling; D009566:Nitrates / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010472:Perchlorates / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D013861:Thiocyanates / Q000494:pharmacology
D000085:Acetates; D000838:Anions; D001639:Bicarbonates; D002087:Butyrates; D002704:Chlorates; D006885:Hydroxybutyrates; D007773:Lactates; D009566:Nitrates; D010472:Perchlorates; D010710:Phosphates; D013861:Thiocyanates; D001151:Arsenic; D002118:Calcium