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Glancy 2013 Biochemistry

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Publications in the MiPMap
Glancy B, Willis WT, Chess DJ, Balaban RS (2013) Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria. Biochemistry 52:2793-809.

» PMID: 23547908 Open Access

Glancy B, Willis WT, Chess DJ, Balaban RS (2013) Biochemistry

Abstract: Calcium is believed to regulate mitochondrial oxidative phosphorylation, thereby contributing to the maintenance of cellular energy homeostasis. Skeletal muscle, with an energy conversion dynamic range of up to 100-fold, is an extreme case for evaluating the cellular balance of ATP production and consumption. This study examined the role of Ca(2+) in the entire oxidative phosphorylation reaction network in isolated skeletal muscle mitochondria and attempted to extrapolate these results back to the muscle, in vivo. Kinetic analysis was conducted to evaluate the dose-response effect of Ca(2+) on the maximal velocity of oxidative phosphorylation (VmaxO) and the ADP affinity. Force-flow analysis evaluated the interplay between energetic driving forces and flux to determine the conductance, or effective activity, of individual steps within oxidative phosphorylation. Measured driving forces [extramitochondrial phosphorylation potential (ΔGATP), membrane potential, and redox states of NADH and cytochromes bH, bL, c1, c, and a,a3] were compared with flux (oxygen consumption) at 37 °C; 840 nM Ca(2+) generated an ∼2-fold increase in VmaxO with no change in ADP affinity (∼43 μM). Force-flow analysis revealed that Ca(2+) activation of VmaxO was distributed throughout the oxidative phosphorylation reaction sequence. Specifically, Ca(2+) increased the conductance of Complex IV (2.3-fold), Complexes I and III (2.2-fold), ATP production/transport (2.4-fold), and fuel transport/dehydrogenases (1.7-fold). These data support the notion that Ca(2+) activates the entire muscle oxidative phosphorylation cascade, while extrapolation of these data to the exercising muscle predicts a significant role of Ca(2+) in maintaining cellular energy homeostasis. Keywords: Metabolic homeostasis, Bioenergetics, Electron transport chain, Cytochrome oxidase, Thermodynamic stoichiometry


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Tissue;cell: Skeletal muscle  Preparation: Intact organ, Isolated mitochondria  Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, TCA cycle and matrix dehydrogenases  Regulation: ADP, Calcium, mt-Membrane potential, Phosphate, Redox state  Coupling state: OXPHOS, ET  Pathway: N, CIV