title: Lysosomal myopathies: an excessive build-up in autophagosomes is too much to handle.
abstract: Lysosomes are membrane-bound acidic organelles that contain hydrolases used for intracellular digestion of various macromolecules in a process generally referred to as autophagy. In normal skeletal and cardiac muscles, lysosomes usually appear morphologically unremarkable and thus are not readily visible on light microscopy. In distinct neuromuscular disorders, however, lysosomes have been shown to be structurally abnormal and functionally impaired, leading to the accumulation of autophagic vacuoles in myofibers. More specifically, there are myopathies in which buildup of these autophagic vacuoles seem to predominate the pathological picture. In such conditions, autophagy is considered not merely a secondary event, but a phenomenon that actually contributes to disease pathomechanism and/or progression. At present, there are two disorders in the muscle which are associated with primary defect in lysosomal proteins, namely Danon disease and Pompe disease. Other myopathies which have prominent autophagy in the skeletal muscle include X-linked myopathy with excessive autophagy (XMEA). In this review, these disorders are briefly characterized, and the role of autophagy in the context of the pathomechanism of these disorders is highlighted.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
authors.forename: May Christine
authors.initials: MC
authors.lastname: Malicdan
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D001343:Autophagy / Q000502:physiology*; D006009:Glycogen Storage Disease Type II / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000172:deficiency; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000145:classification / Q000473:pathology*
chemical_list: D051907:Lysosomal Membrane Proteins