Control of Respiration in Intact Muscle

Abstract

We believe that the hydrolysis of ATP provides the free energy for all cell function, and we know that the ultimate source of almost all ATP produced in muscle is oxidative metabolism (Fig. 1). We’d like to know, in as much detail as possible, the mechanism coupling these two fundamental processes, whereby a change in the rate of ATP utilization leads to a change in the rate of oxidative phosphorylation. That brings me to my second reason for choosing the first figure. In what can be thought of as perhaps the first attempt to model the control of respiration in muscle, Chance and Connelly’ used a scheme little more complicated than this. Having determined the responses of isolated mitochondria to limiting concentrations of ADP or inorganic phosphate (Pi), they assumed that the rest of the cell could be represented simply as an ATPase. I mention this not to impugn or embarass two distinguished scientists, but to illustrate the point that, in general, workers in this field have shown a surprising lack of awareness of, or concern for, events occurring outside the mitochondrial inner membrane. To the extent that this audience shares that attitude, I hope to correct it. Fig. 2 shows a current, schematic description of the reactions believed to couple oxidative phosphorylation to ATP hydrolysis, which I hope will meet with everyone’s approval.