Mitochondrial Dysfunction in Neuromuscular Disorders

• Published in: Seminars in pediatric neurology Vol. 20; no. 3; pp. 202 - 215
• Main Authors: Katsetos, Christos D., MD, PhD, FRCPath, Koutzaki, Sirma, MS, Melvin, Joseph J., DO
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2013
• Subjects: Animals; Humans; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial Diseases - complications; Mitochondrial Diseases - drug therapy; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Membrane Transport Proteins - drug effects; Molecular Targeted Therapy; Neurology; Neuromuscular Diseases - chemically induced; Neuromuscular Diseases - complications; Neuromuscular Diseases - drug therapy; Neuromuscular Diseases - genetics; Neuromuscular Diseases - metabolism; Pediatrics
• ISSN: 1071-9091; 1558-0776
• DOI: 10.1016/j.spen.2013.10.010

This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.