Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria

Brian Glancy, Wayne T. Willis, David J. Chess, Robert S. Balaban

Research output: Contribution to journalArticlepeer-review

221 Scopus citations


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 Ca2+ 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 Ca2+ on the maximal velocity of oxidative phosphorylation (V maxO) 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,a 3] were compared with flux (oxygen consumption) at 37 C; 840 nM Ca2+ generated an ∼2-fold increase in VmaxO with no change in ADP affinity (∼43 μM). Force-flow analysis revealed that Ca2+ activation of VmaxO was distributed throughout the oxidative phosphorylation reaction sequence. Specifically, Ca2+ 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 Ca2+ activates the entire muscle oxidative phosphorylation cascade, while extrapolation of these data to the exercising muscle predicts a significant role of Ca2+ in maintaining cellular energy homeostasis.

Original languageEnglish (US)
Pages (from-to)2793-2809
Number of pages17
Issue number16
StatePublished - Apr 23 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria'. Together they form a unique fingerprint.

Cite this