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

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The role of Ca2+ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca2+ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa3 ratio. The half-maximal concentration (K1/2) of SR ATPase was 335 nM Ca2+. The ATP synthesis dependence was similar with a K1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca2+ 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 Ca2+ concentrations (0 to ∼500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca2+ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca2+ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.

Original languageEnglish (US)
Pages (from-to)C285-C293
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number2 53-2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Adenosine 5′-triphosphate
  • Calcium-adenosinetriphosphatase
  • Energy metabolism
  • Porcine heart
  • Reduced nicotinamide adenine dinucleotide

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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