Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy

Skeletal muscle mitochondria were isolated from 33 dystrophic hamsters of the BIO 14.6 strain, aged 265 ± 13 (S.E.) days, by glass-on-glass homogenization in a sucrose–EDTA medium in the absence of the proteinase Nagarse. These organelles utilized O2 at half the normal rate with pyruvate/fumarate or palmitate as substrate in a manometric test system and exhibited decreased P/O ratios and phosphorylation rates with pyruvate/fumarate. In polarographic experiments the mitochondria from dystrophic muscle, supplemented with L-malate, had significantly depressed O2 uptake rates, respiratory control ratios, and phosphorylation rates with pyruvate, palmityl-L-carnitine, and acetyl-L-carnitine as substrates and low ADP/O ratios with pyruvate and palmityl-L-carnitine. Since the severity of the respiratory depression was similar with the three substrates, it appeared that the defect lay beyond acetyl-CoA in their common degradative pathway. Judging from the rapid rate of succinate and NADH oxidation, the respiratory chain was unimpaired. It was concluded that a defect was present in the tricarboxylic acid cycle of muscle mitochondria isolated without Nagarse from older dystrophic hamsters of the BIO 14.6 strain and that the defect was accompanied by a loose coupling of oxidative phosphorylation.