@article{SchumannSchallerBelcheetal.2021,
  author    = {Anke Schumann and Kristin Schaller and V{\´e}ronique Belche and Markus Cybulla and Sarah C. Gr{\"u}nert and Nicolai Moers and J{\"o}rn O. Sass and Andres Kaech and Luciana Hannibal and Ute Spiekerkoetter},
  title     = {Defective lysosomal storage in Fabry Disease modifies mitochondrial structure, metabolism and turnover in renal epithelial cells},
  series   = {Journal of Inherited Metabolic Disease},
  volume    = {44},
  publisher = {John Wiley \& Sons Ltd},
  address   = {Hoboken, NJ, USA},
  issn      = {0141-8955},
  doi       = {10.1002/jimd.12373},
  url       = {https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-53487},
  pages     = {1039 -- 1050},
  year      = {2021},
  abstract  = {Fabry disease (FD) is an X‐linked lysosomal storage disorder. Deficiency of the lysosomal enzyme alpha‐galactosidase (GLA) leads to accumulation of potentially toxic globotriaosylceramide (Gb3) on a multisystem level. Cardiac and cerebrovascular abnormalities as well as progressive renal failure are severe, life‐threatening long‐term complications. The complete pathophysiology of chronic kidney disease (CKD) in FD and the role of tubular involvement for its progression are unclear. We established human renal tubular epithelial cell lines from the urine of male FD patients and male controls. The renal tubular system is rich in mitochondria and involved in transport processes at high energy costs. Our studies revealed fragmented mitochondria with disrupted cristae structure in FD patient cells. Oxidative stress levels were elevated and oxidative phosphorylation was up‐regulated in FD pointing at enhanced energetic needs. Mitochondrial homeostasis and energy metabolism revealed major changes as evidenced by differences in mitochondrial number, energy production and fuel consumption. The changes were accompanied by activation of the autophagy machinery in FD. Sirtuin1, an important sensor of (renal) metabolic stress and modifier of different defense pathways, was highly expressed in FD. Our data show that lysosomal FD impairs mitochondrial function and results in severe disturbance of mitochondrial energy metabolism in renal cells. This insight on a tissue‐specific level points to new therapeutic targets which might enhance treatment efficacy.},
  language  = {en}
}