Ultrastructural Changes in Skeletal Muscle of Infants with Mitochondrial Respiratory Chain Complex I Defects

BACKGROUND AND PURPOSE: The pathogenesis of mitochondrial disease (MD) involves the disruption of cellular energy metabolism, which results from defects in the mitochondrial respiratory chain complex (MRC). We investigated whether infants with MRC I defects showed ultrastructural changes in skeletal muscle. METHODS: Twelve infants were enrolled in this study. They were initially evaluated for unexplained neurodegenerative symptoms, myopathies, or other progressive multiorgan involvement, and underwent muscle biopsies when MD was suspected. Muscle tissue samples were subjected to biochemical enzyme assays and observation by transmission electron microscopy. We compared and analyzed the ultrastructure of skeletal muscle tissues obtained from patients with and without MRC I defects. RESULTS: Biochemical enzyme assays confirmed the presence of MRC I defects in 7 of the 12 patients. Larger mitochondria, lipid droplets, and fused structures between the outer mitochondrial membrane and lipid droplets were observed in the skeletal muscles of patients with MRC I defects. CONCLUSIONS: Mitochondrial functional defects in MRC I disrupt certain activities related to adenosine triphosphate synthesis that produce changes in the skeletal muscle. The ultrastructural changes observed in the infants in this study might serve as unique markers for the detection of MD.

Effects of a Low Calcium Diet and Oxalate Intake on Calcium Deposits in Soft Tissues and Bone Metabolism in Ovariectomized Rats

It is controversial whether low calcium intake, commonly associated with osteoporosis, results in calcium accumulation in soft tissues. This study was conducted to investigate the effects of low calcium (Ca) and oxalate (ox) intake on soft-tissue Ca deposits and bone metabolism in ovariectomized (ovx) rats. Eight week old female Sprague-Dawley rats were ovariectomized and divided into four groups. The rats were fed experimental diets containing low (0.1%, w/w) or normal (0.5%, w/w) Ca with or without sodium oxalate (1%, w/w); Sham/NCa, Ovx/NCa, Ovx/LCa, Ovx/NCa-ox, Ovx/LCa-ox for 6 weeks. All ovx rats showed a remarkable increase in body and tissue weight, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, blood urea nitrogen, alkaline phosphatase, and decreases in weight, ash, and Ca contents, as well as bone breaking force compared to those in sham rats. Serum Ca concentration was not significantly affected by dietary Ca levels or ox intake. Kidney Ca, ox acid content, and microscopic Ca deposition increased remarkably in the Ovx/LCa-ox group compared to those in the other groups. Ca content in the spleen and aorta also increased significantly, but the weight contents, Ca, bone breaking force, and Ca and oxalic acid in feces decreased significantly in the Ovx/LCa-ox group. Serum parathyroid hormone levels were not significantly different among the groups. These results indicate that low Ca intake decreased bone mineral content and increased Ca deposits in soft tissues, which was aggravated by ox intake in ovx rats. Thus, high ox intake may result in a kidney disorder in patients with osteoporosis who eat a low Ca diet.