title: Open-Loop Control of Oxidative Phosphorylation in Skeletal and Cardiac Muscle Mitochondria by Ca(2.).
abstract: In cardiac muscle, mitochondrial ATP synthesis is driven by demand for ATP through feedback from the products of ATP hydrolysis. However, in skeletal muscle at higher workloads there is an apparent contribution of open-loop stimulation of ATP synthesis. Open-loop control is defined as modulation of flux through a biochemical pathway by a moiety, which is not a reactant or a product of the biochemical reactions in the pathway. The role of calcium, which is known to stimulate the activity of mitochondrial dehydrogenases, as an open-loop controller, was investigated in isolated cardiac and skeletal muscle mitochondria. The kinetics of NADH synthesis and respiration, feedback from ATP hydrolysis products, and stimulation by calcium were characterized in isolated mitochondria to test the hypothesis that calcium has a stimulatory role in skeletal muscle mitochondria not apparent in cardiac mitochondria. A range of respiratory states were obtained in cardiac and skeletal muscle mitochondria utilizing physiologically relevant concentrations of pyruvate and malate, and flux of respiration, NAD(P)H fluorescence, and rhodamine 123 fluorescence were measured over a range of extra mitochondrial calcium concentrations. We found that under these conditions calcium stimulates NADH synthesis in skeletal muscle mitochondria but not in cardiac mitochondria.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan. Electronic address: kalyanv@umich.edu.
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Vinnakota
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singhal
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Françoise
authors.initials: F
authors.lastname: Van den Bergh
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Bagher-Oskouei
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Wiseman
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Beard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019069:Cell Respiration; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology*; D009243:NAD / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009243:NAD; D002118:Calcium