title: Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders.
abstract: Lysosomal storage disorders (LSDs) are rare inherited debilitating and often fatal disorders. Caused by mutations affecting lysosomal proteins, LSDs are characterized by the accumulation of undegraded material in lysosomes and by lysosomal dysfunction. Although LSDs are multisystemic diseases, the majority display neurologic symptoms and neurodegeneration. Only recently has a role emerged for mitochondrial dysfunction in the pathophysiology of LSDs, suggesting an impact of lysosomal dysfunction on mitochondria. Moreover, mitochondrial damage may also cause lysosomal dysfunction, further supporting the activity of common signaling pathways and crosstalk between the two organelles. In this review we explore the mechanisms linking lysosomal and mitochondrial dysfunction to assess whether specific mitochondrial pathways represent a new therapeutic frontier in the management of LSDs.
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London (UCL), Gower Street, London WC1E 6BT, UK.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Plotegher
authors.affiliation: Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London (UCL), Gower Street, London WC1E 6BT, UK. Electronic address: m.duchen@ucl.ac.uk.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
mesh_terms: D000818:Animals; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000209:etiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; C018589:lysosomal proteins