Mitochondrial dynamics of proximal tubular epithelial cells in nephropathic cystinosis

Domenico De Rasmo, Anna Signorile, Ester De Leo, Elena V. Polishchuk, Anna Ferretta, Roberto Raso, Silvia Russo, Roman Polishchuk, Francesco Emma, Francesco Bellomo

Research output: Contribution to journalArticlepeer-review


Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in CTNS gene leading to Fanconi syndrome. Independent studies reported defective clearance of damaged mitochondria and mitochondrial fragmentation in cystinosis. Proteins involved in the mitochondrial dynamics and the mitochondrial ultrastructure were analyzed in CTNS−/− cells treated with cysteamine, the only drug currently used in the therapy for cystinosis but ineffective to treat Fanconi syndrome. CTNS−/− cells showed an overexpression of parkin associated with deregulation of ubiquitination of mitofusin 2 and fission 1 proteins, an altered proteolytic processing of optic atrophy 1 (OPA1), and a decreased OPA1 oligomerization. According to molecular findings, the analysis of electron microscopy images showed a decrease of mitochondrial cristae number and an increase of cristae lumen and cristae junction width. Cysteamine treatment restored the fission 1 ubiquitination, the mitochondrial size, number and lumen of cristae, but had no effect on cristae junction width, making CTNS−/− tubular cells more susceptible to apoptotic stimuli.

Original languageEnglish
Article number192
JournalInternational Journal of Molecular Sciences
Issue number1
Publication statusE-pub ahead of print - 2019


  • Cysteamine
  • Fanconi syndrome
  • Mitochondrial cristae
  • Mitochondrial dynamics
  • Mitochondrial fission
  • Mitochondrial fusion
  • Nephropathic cystinosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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