Feedback Regulation and Time Hierarchy of Oxidative Phosphorylation in Cardiac Mitochondria

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2016 Feb 25

PMID 26910434

Citations 20

Authors

Kalyan C Vinnakota

Jason N Bazil

Francoise Van den Bergh

Robert W Wiseman

Daniel A Beard

Affiliations

Soon will be listed here.

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.

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