Effects of thyroid hormones on oxidative phosphorylation

Abstract

Introduction I t has long been known that the administration of thyroid hormones results in increases in oxygen consumption and in heat production, and that subnormal levels of thyroid hormones result in the opposite effects. Mitochondria from the livers of rats that have been treated with thyroid hormones ('hyperthyroid mitochondria') have oxygen-consurnption rates that are greater than the rates determined for euthyroid controls, and mitochondria from the livers of hypothyroid rats ('hypothyroid mitochondria') have lower oxygen-consumption rates than euthyroid controls [ 1 , 2). These changes in oxygen-consumption rate are also observed in hepatocytes that have been isolated from hyperthyroid and from hypothyroid rats 131. Such changes are thought to be an important part of the thyroid-horriione-induced changes in metabolic rate and in heat production (4-61. The focus of this brief review is on the effects of thyroid hormones on oxidative ptiosptiorylation at the levels of liver mitochondria and of hepatocytes. 'Hie effects o f thyroid hormones on oxygen consumption and on energy metabolism in mitochondria and in cells have been categorized into short-term and long-term effects. The mechanisms and the sites of action for the shortand long-term effects of thyroid hormones are discussed in another paper in this colloquium (S. Soboll, this colloquium). The discussion here will be limited to the long-term effects (that is, occurring after a period of 24 h) in rats; emphasis will be placed on the results of recent studies that have used the top-down elasticity-analysis approach (described in M. I). I h n d , I,. I;. Chien and I). F. S. Rolfe, this colloquium) to identify the important sites of action of thyroid hormones. Despite there being a substantial literature on the effects of thyroid hormones on oxidative phosphorylation, it is still not clear which of the effects on component enzymes and on pathways are quantitatively the most important. For example, it has