Cystinosin is a melanosomal protein that regulates melanin synthesis

Christine Chiaverini, Laura Sillard, Enrica Flori, Shosuke Ito, Stefania Briganti, Kazumasa Wakamatsu, Eric Fontas, Etienne Berard, Mathilde Cailliez, Pierre Cochat, Michel Foulard, Geneviève Guest, Patrick Niaudet, Mauro Picardo, François Xavier Bernard, Corinne Antignac, Jean Paul Ortonne, Robert Ballotti

Research output: Contribution to journalArticlepeer-review


Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H+ symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.

Original languageEnglish
Pages (from-to)3779-3789
Number of pages11
JournalFASEB Journal
Issue number9
Publication statusPublished - Sep 2012


  • Cystinosis
  • Melanocyte
  • Melanogenesis
  • Pigmentation
  • Tyrosinase

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology


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