Thyroxine-Binding by Muscle Mitochondria from Normal and Genetically Dystrophic Chickens 1

Abstract

There are disparate observations in the literature which suggest that respiration is abnormal in genetically dystrophic muscle and that the course of the disease may be temporarily retarded by treatments which increase the availability of oxygen to the tissue or facilitate the biosynthesis of ATP by the oxidative-phosphorylation system. Mitochondria from dystrophic muscle are abnormal morphologically (1, 2). Mitochondria from dystrophic chicken muscle show an elevated rate of oxygen uptake when incubated in the presence of Mg²⁺ and ATP (3). A low ATP level in dystrophic muscle (4, 5) and the possibility that a low ATP:ADP ratio results in a swelling of the respiratory assembly in mitochondria (6) led to the suggestion (3) that accelerated loss of ATP from mitochondria in dystrophic muscle is responsible for the abnormal permeability of the mitochondrial membrane (7) and the altered microscopic appearance. In studies with canary and rat liver mitochondria thyroxine was found to stimulate ATPase activity (8-10), concomitantly with the induction of mitochondrial swelling. In view of the above it is interesting that administration of large doses of thyroxine to dystrophic mice improves movement (11), and that a high-oxygen environment retards the progress of muscular dystrophy in chickens (12, 13) although only temporarily (14). Treatment of dystrophic mice with coenzyme Q has also been reported to improve their condition (15, 16) and it may be significant that experimental thyrotoxicosis markedly increases the level of coenzyme Q in rat liver mitochondria (17). Evidence of mitochondrial abnormality in muscular dystrophy and the effect, albeit temporary, on the progress of the disease of treatments which appear to relate to augmentation of energy available from mitochondrial function, suggested the following experiments to determine if thyroxine-binding is normal in the mitochondria of dystrophic muscle.