title: Mitochondrial dysfunction in neuromuscular disorders.
abstract: 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.
authors: Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA; Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA. Electronic address: Christos.Katsetos@drexelmed.edu.
authors: Christos D
authors: CD
authors: Katsetos
authors: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA.
authors: Sirma
authors: S
authors: Koutzaki
authors: Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA; Department of Neurology, Drexel University College of Medicine, Philadelphia, PA.
authors: Joseph J
authors: JJ
authors: Melvin
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D058990:Molecular Targeted Therapy; D009468:Neuromuscular Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore