Regulation of cardiac cellular bioenergetics: mechanisms and consequences

Abstract

The regulation of cardiac cellular bioenergetics is critical for maintaining normal cell function, yet the nature of this regulation is not fully understood. Different mechanisms have been proposed to explain how mitochondrial ATP production is regulated to match changing cellular energy demand while metabolite concentrations are maintained. We have developed an integrated mathematical model of cardiac cellular bioenergetics, electrophysiology, and mechanics to test whether stimulation of the dehydrogenase flux by Ca(2+) or Pi, or stimulation of complex III by Pi can increase the rate of mitochondrial ATP production above that determined by substrate availability (ADP and Pi). Using the mode..