title: Mg2+ control of respiration in isolated rat liver mitochondria.
abstract: The role of endogenous mitochondrial Mg2+ as a potential regulator of mitochondrial dehydrogenase activity, and therefore of cellular respiration, was measured in isolated mitochondria containing matrix Ca2+ and Mg2+ levels resembling those occurring in vivo. Ca2+ and Mg2+ depletion was carried out using the cation ionophore A23187 in the presence or absence of the Ca2+ uniporter inhibitor ruthenium red (RR). Divalent cation depletion inhibits the oxidation of alpha-ketoglutarate or pyruvate in states 4 and 3, slows uncoupled respiration and results in decreased membrane potential. Since the addition of Mg2+ could not restore respiration, these dehydrogenases appear not to be regulated by Mg2+. In contrast, similar cation depletion stimulates succinate dehydrogenase (or glutamate dehydrogenase) in state 4 without decreasing membrane potential. The addition of RR caused authentic uncoupling, accompanied by a decrease in membrane potential and an increase in membrane permeability. These effects could be completely reversed by Mg2+. These and other data, showing that Mg2+ depletion results in a change of respiration depending on the substrate oxidized and the metabolic state, indicate that Mg2+ removal may have direct and indirect effects on mitochondrial respiration. A clear direct effect is the stimulation of succinate or glutamate dehydrogenase by decreasing matrix Mg2+. Hence, changes in matrix Mg2+ (in addition to those of Ca2+) could be of great consequence, not only for the control of respiration but also for metabolic pathways affected by changes in concentrations of matrix substrates.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
authors.forename: A
authors.initials: A
authors.lastname: Panov
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption; D010539:Permeability / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D007476:Ionophores; D007656:Ketoglutaric Acids; D013386:Succinates; D012402:Rotenone; D012430:Ruthenium Red; D014634:Valinomycin; D000001:Calcimycin; D018698:Glutamic Acid; D004533:Egtazic Acid; D006859:Hydrogen; D019802:Succinic Acid; D008274:Magnesium; D011188:Potassium; D002118:Calcium