title: Feedback Regulation and Time Hierarchy of Oxidative Phosphorylation in Cardiac Mitochondria.
abstract: To determine how oxidative ATP synthesis is regulated in the heart, the responses of cardiac mitochondria oxidizing pyruvate to alterations in [ATP], [ADP], and inorganic phosphate ([Pi]) were characterized over a range of steady-state levels of extramitochondrial [ATP], [ADP], and [Pi]. Evolution of the steady states of the measured variables with the flux of respiration shows that: (1) a higher phosphorylation potential is achieved by mitochondria at higher [Pi] for a given flux of respiration; (2) the time hierarchy of oxidative phosphorylation is given by phosphorylation subsystem, electron transport chain, and substrate dehydrogenation subsystems listed in increasing order of their response times; (3) the matrix ATP hydrolysis mass action ratio [ADP] × [Pi]/[ATP] provides feedback to the substrate dehydrogenation flux over the entire range of respiratory flux examined in this study; and finally, (4) contrary to previous models of regulation of oxidative phosphorylation, [Pi] does not modulate the activity of complex III.
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: Jason N
authors.initials: JN
authors.lastname: Bazil
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 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: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019069:Cell Respiration; D025461:Feedback, Physiological; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010710:Phosphates / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013389:Succinate-CoA Ligases / Q000378:metabolism; D013696:Temperature
chemical_list: D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D013389:Succinate-CoA Ligases