Boelens 2013 J Bioenerg Biomembr

Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF (2015) Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria. J Bioenerg Biomembr 45:203-18.

» PMID: 23456198

Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF (2015) J Bioenerg Biomembr

Abstract: Cardiac mitochondrial matrix (m) free Ca²⁺ ([Ca²⁺]m) increases primarily by Ca²⁺ uptake through the Ca²⁺ uniporter (CU). Ca²⁺ uptake via the CU is attenuated by extra-matrix (e) Mg²⁺ ([Mg²⁺]e). How [Ca²⁺]m is dynamically modulated by interacting physiological levels of [Ca²⁺]e and [Mg²⁺]e and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg²⁺]e modulates Ca²⁺ uptake via the CU, it also alters bioenergetics in a matrix Ca²⁺-induced and matrix Ca²⁺-independent manner. To test this, we measured changes in [Ca²⁺]e, [Ca²⁺]m, [Mg²⁺]e and [Mg²⁺]m spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl₂ (0-0.6 mM; 1 mM EGTA buffer) with/without added MgCl₂ (0-2 mM). In parallel, we assessed effects of added CaCl₂ and MgCl₂ on NADH, membrane potential (ΔΨm), and respiration. We found that ≥0.125 mM MgCl₂ significantly attenuated CU-mediated Ca²⁺ uptake and [Ca²⁺]m. Incremental [Mg²⁺]e did not reduce initial Ca²⁺ uptake but attenuated the subsequent slower Ca²⁺ uptake, so that [Ca²⁺]m remained unaltered over time. Adding CaCl₂ without MgCl₂ to attain a [Ca²⁺]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca²⁺]m did not additionally enhance NADH oxidation or respiration. Adding MgCl₂ did not increase [Mg²⁺]m but it altered bioenergetics by its direct effect to decrease Ca²⁺ uptake. However, at a given [Ca²⁺]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg²⁺]e. Thus, [Mg²⁺]e without a change in [Mg²⁺]m can modulate bioenergetics independently of CU-mediated Ca²⁺ transport. • Keywords: Cardiac mitochondria, Inner mitochondrial membrane, Bioenergetics, Ca²⁺ uniporter, Ca²⁺ uptake, Mg²⁺ inhibition

Labels: MiParea: Respiration, mt-Membrane 

Organism: Guinea pig  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: Calcium  Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. 

HRR: Oxygraph-2k 

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