Role of Amyloid Beta in Mitochondrial Function and Dynamics in Skeletal Muscle

Abstract

Spontaneous inclusion body myositis (sIBM) is an inflammatory myopathy characterized by progressive muscle weakness, resulting in loss of function and mobility. Skeletal muscle from patients with sIBM display mitochondrial abnormalities including DNA deletions, cytochrome c oxidase deficiency, morphological deformities, and inclusion bodies. It has been suggested that amyloid β (Abeta) accumulation may be critical to pathophysiology of the disease. To understand the role of Abeta in mitochondrial function and dynamics in skeletal muscle, L6 rat and human primary skeletal muscle cells were treated with 200pg or 100nM of Abeta for 4 hours. Immediately following treatment, oxygen consumption and protein content of optic atrophy protein 1 (OPA1) and dynamin related protein 1 (DRP1) were assessed. Abeta resulted in a significant decline in maximally stimulated oxygen consumption, which was observed in conjunction with a decline and increase in OPA1 and DRP1 protein, respectively, and increases in interleukin 6 and monocyte chemotactic protein 1 mRNA. These results demonstrate that Abeta causes mitochondrial dysfunction, inflammation and alters regulators of mitochondrial dynamics in skeletal muscle.