Mitochondrial dynamics of proximal tubular epithelial cells in nephropathic cystinosis: International Journal of Molecular Sciences

D.D. Rasmo, A. Signorile, E. De Leo, E.V. Polishchuk, A. Ferretta, R. Raso, S. Russo, R. Polishchuk, F. Emma, F. 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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
JournalInt. J. Mol. Sci.
Issue number1
Publication statusPublished - 2020


  • Cysteamine
  • Fanconi syndrome
  • Mitochondrial cristae
  • Mitochondrial dynamics
  • Mitochondrial fission
  • Mitochondrial fusion
  • Nephropathic cystinosis
  • dynamin I
  • mercaptamine
  • mitochondrial fission 1 protein
  • mitochondrial protein
  • mitofusin 2
  • outer membrane protein
  • parkin
  • ubiquitin thiolesterase
  • unclassified drug
  • amino acid transporter
  • CTNS protein, human
  • FIS1 protein, human
  • guanosine triphosphatase
  • membrane protein
  • MFN2 protein, human
  • OPA1 protein, human
  • ubiquitin protein ligase
  • apoptosis
  • Article
  • autosomal dominant optic atrophy
  • cell ultrastructure
  • chemoluminescence
  • CTNS gene
  • cystinosis
  • electron microscopy
  • epithelium cell
  • gene
  • gene overexpression
  • human
  • human cell
  • mitochondrial dynamics
  • mitochondrial membrane
  • mitochondrial volume
  • nephropathic cystinosis
  • oligomerization
  • phenotype
  • protein phosphorylation
  • transmission electron microscopy
  • ubiquitination
  • Western blotting
  • cell culture
  • cytology
  • drug effect
  • genetics
  • kidney proximal tubule
  • metabolism
  • mitochondrion
  • Amino Acid Transport Systems, Neutral
  • Cells, Cultured
  • Cystinosis
  • Epithelial Cells
  • GTP Phosphohydrolases
  • Humans
  • Kidney Tubules, Proximal
  • Membrane Proteins
  • Mitochondria
  • Mitochondrial Dynamics
  • Mitochondrial Proteins
  • Ubiquitin-Protein Ligases
  • Ubiquitination


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