Altered mTOR signalling in nephropathic cystinosis

Ekaterina A. Ivanova, Lambertus P. van Den Heuvel, Mohamed A. Elmonem, Humbert de Smedt, Ludwig Missiaen, Anna Pastore, Djalila Mekahli, Greet Bultynck, Elena N. Levtchenko

Research output: Contribution to journalArticlepeer-review


Lysosomes play a central role in regulating autophagy via activation of mammalian target of rapamycin complex 1 (mTORC1). We examined mTORC1 signalling in the lysosomal storage disease nephropathic cystinosis (MIM 219800), in which accumulation of autophagy markers has been previously demonstrated. Cystinosis is caused by mutations in the lysosomal cystine transporter cystinosin and initially affects kidney proximal tubules causing renal Fanconi syndrome, followed by a gradual development of end-stage renal disease and extrarenal complications. Using proximal tubular kidney cells obtained from healthy donors and from cystinotic patients, we demonstrate that cystinosin deficiency is associated with a perturbed mTORC1 signalling, delayed reactivation of mTORC1 after starvation and abnormal lysosomal retention of mTOR during starvation. These effects could not be reversed by treatment with cystine-depleting drug cysteamine. Altered mTORC1 signalling can contribute to the development of proximal tubular dysfunction in cystinosis and points to new possibilities in therapeutic intervention through modulation of mTORC-dependent signalling cascades.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of Inherited Metabolic Disease
Publication statusAccepted/In press - Feb 24 2016

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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