Larry R. Jones

School of Medicine, Medicine, Cardiology

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Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro

Robert S. Balaban; Salil Bose; Stephanie A. French; Paul R. Territo (Profiled Author: Paul Territo)

American Journal of Physiology - Cell Physiology. 2003;284(2 53-2):C285-C293.

The role of Ca ²⁺ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca ²⁺ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa 3 ratio. The half-maximal concentration (K 1/2) of SR ATPase was 335 nM Ca ²⁺. The ATP synthesis dependence was similar with a K 1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca ²⁺ increased thapsigargin-sensitive ATP production (maximum ∼5-fold) with minimal changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH). NADH concentration remained stable despite graded increases in NADH turnover induced over a wide range of Ca ²⁺ concentrations (0 to ∼500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca ²⁺ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca ²⁺ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.

PMID: 12529248    

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