title: Lysosomal dysfunction in muscle with special reference to glycogen storage disease type II.
abstract: The importance of proper lysosomal activity in cell and tissue homeostasis is underlined by "experiments of nature", i.e. genetic defects in one of the at least 40 lysosomal enzymes/proteins present in the human cell. The complete lack of 1-4 alpha-glucosidase (glycogen storage disease type II (GSD II) or Pompe disease) is life-threatening. Patients suffering from GSD II commonly die before the age of 2 years because of cardiorespiratory insufficiency. Striated muscle cells appear to be particularly vulnerable in GSD II. The high cytoplasmic glycogen content in muscle cells most likely gives rise to a high rate of glycogen engulfment by the lysosomes. The polysaccharides become subsequently trapped in these organelles when 1-4 alpha-glucosidase activity is absent. During the course of the disease, muscle wasting occurs. It is hypothesised that the gradual loss of muscle mass is caused by a combination of disuse atrophy and lipofuscine-mediated apoptosis of myocytes. Moreover, we hypothesise that in the remaining skeletal muscle cells, longitudinal transmission of force is hampered by swollen lysosomes, clustering of non-contractile material and focal regions with degraded contractile proteins, which results in muscle weakness.
authors.affiliation: Department of Movement Sciences, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Reinout.Hesselink@BW.Unimass.nl
authors.forename: Reinout P
authors.initials: RP
authors.lastname: Hesselink
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Wagenmakers
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Drost
authors.forename: Ger J
authors.initials: GJ
authors.lastname: Van der Vusse
mesh_terms: D000818:Animals; D005087:Glucan 1,4-alpha-Glucosidase / Q000172:deficiency / Q000235:genetics; D006009:Glycogen Storage Disease Type II / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008062:Lipofuscin / Q000096:biosynthesis; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D000520:alpha-Glucosidases
chemical_list: D008062:Lipofuscin; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase