Regulation of ATP Production by Mitochondria

Cardiac ventricular myocytes work continuously but have minimal intracellular energy reserves sufficient for less than 30 seconds of work. To compensate for this energetic vulnerability, rapid and accurate real-time ATP production is essential, regulated by a stringent feedback-control system. Half of the required feedback-control system has been elucidated and updated recently showing how cellular and mitochondrial [Ca2+] control mitochondrial ATP production. Here we present critical new information on the second half of the feedback-control system which senses the amounts of energy consumed and carbon-based food-stock processed by mitochondria to synthesize ATP. We show that the pivotal new sensor that enables this process is soluble adenylyl cyclase, which resides in the mitochondrial intermembrane space and drives additional ATP production by mitochondria through the activation of a novel signaling cascade.