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

Abstract

Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy. Can. J. Biochem. 48, 1037Biochem. 48, -1042Biochem. 48, (1970.Skeletal muscle mitochondria were isolated from 33 dystrophic hamsters of the BI8 14.6 strain, aged 265 f 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 pyruvatelfumarate or palmitate as substrate in a manometric test system and exhibited decreased P/Q ratios and phospkorylation rates with pyruvateifumarate. In pslarographic 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-~~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 NABH 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 BZO 14.6 strain and that the defect was accompanied by a loose coupling of oxidative phosphorylation.

Nucleic Acids and Lysosomal Hydrolases in the Skeletal Muscle of BIO 14.6 Dystrophic Hamsters

“…Attempts to find a correlation between the present findings and the severity of the disturbance in mitochondrial respiration and oxidative phosphorylation in hamsters of this age [13] were unsuccessful. How ever, as reported recently [28] a relationship does appear to exist in younger BIO 14.6 hamsters between the severity of a magnesiumresponsive mitochondrial defect and the frequency and extent of the localized regions of necrosis, visible as the longitudinal white streaks in the skeletal muscle described here.…”

“…In view of the normal levels of collagen and non-collagen protein in the present dystrophic hamsters, it should be emphasized that the muscles of animals of this age reveal microscopic evidence [11] of the dystrophic process and yield mitochondria with defective respiration and oxidative phosphorylation [13]. However, in a detailed study of the histopathology of the disease [10] it was noted that cardiac in volvement generally occurred too soon to permit the full progression of the skeletal myopathy to a point where it would resemble the terminal stages of human or murine dystrophy.…”

Some Biochemical Features of White Muscle Disease in Lambs, and the Influence of Selenium

“…The behaviour of isolated mitochondria in hereditary muscular dystrophy, both in the human (Lin et al 1972) and in the experimental animal (Lochner and Brink 1967;Jacobson et al 1970), has been studied. Comparable studies have not, so far, been made in nutritional muscular dystrophy, though a preliminary report of the present experiments has appeared (Godwin 1973).…”

A Toxic Cardiomyopathy Caused byCassia occidentalis. II. Biochemical Studies in Poisoned Rabbits

“…This difference is probably because of the manner of preparation, and, in particular, the use of bacterial proteinase to rid the preparations of myofibrillar remnants. Significant differences in the activities of mitochondria isolated from control and dystrophic hamsters have been demonstrated by the proteinase method and by glass-on-glass homogenization [16,39]. Hamster mitochondria isolated by the proteinase method were considered to have greater overall metabolic integrity and contained significant amounts of endogenous substrate but did have altered ability to utilize particular substrates, such as long-chain fatty acids [16].…”

“…In view of the morphological evidence of mitochondrial damage, the function of mitochondria isolated from the hearts of rabbits poisoned by coffee senna was studied using polarographic techniques to evaluate the status of mitochondrial respiration [5,20]. These techniques have been used by others in the study of various cardio-myopathies [2,[15][16][17]28,33,39]. The studies were combined with examination of several enzymes of the glycolytic and citric acid cycles, and with assays of glycogen and lactate.…”