The effect of thyroxine and related compounds on oxidative phosphorylation.

The finding that oxidative phosphorylation is uncoupled by nitroand halophenols (l-3) has led a number of investigators (4-10) to examine the effect of a physiological halophenol, thyroxine, on this process. Uncoupling of phosphorylation from respiration has been observed following addition of thyroxine and related compounds to suspensions of mitochondria (4-8) as well as in mitochondria isolated from the livers of animals treated with large quantities of thyroxine (4, 5). From such experiments it has been suggested that this uncoupling action, together with compensatory changes in respiration, provides an explanation for the physiological effect of the thyroid hormone (4). In this communication evidence will be presented indicating that the effect of thyroxine and related compounds on the phosphorylation which occurs in intact mitochondria is probably indirect, since these compounds do not uncouple oxidative phosphorylation as it occurs in an isolated enzyme complex separated from extracts of mitochondria. A preliminary account of this work has been published (9).