ArticleNature communications2023
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- Clinical practice recommendations for the diagnosis and management of nephropathic cystinosis.Nature reviews. Nephrology · 2026Review
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- mTORC1-signaling switches megalin function from endocytosis to cell cycle progression.Cellular and molecular life sciences : CMLS · 2026Article
- A zebrafish luminescent biosensor for kidney tubulopathy, metal toxicity and drug screening.Disease models & mechanisms · 2026Article
- Cystinosin regulates NaEMBO reports · 2026Article
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
- Lysosomal Immunoprecipitation (LysoIP) from Cells and Tissues for Metabolomic and Proteomic Analyses.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Autophagy-lysosome flux failure in diabetic kidney disease: tubular vulnerability and cell-state remodeling.Frontiers in endocrinology · 2026Review
- An Isogenic Human Myoblast Cell Model for Cystinosis Myopathy Reveals Alteration of Key Myogenic Regulatory Proteins.Journal of cachexia, sarcopenia and muscle · 2025Article
- Lysosomal reduced thiols are essential for mouse embryonic development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- From Molecular Understanding and Pathophysiology to Disease Management; A Practical Approach and Guidance to the Management of the Ocular Manifestations of Cystinosis.International journal of molecular sciences · 2025Review
- JIP4 deficiency causes a lysosomal storage disease arising from impaired cystine efflux.bioRxiv : the preprint server for biology · 2025Article
- Hypothesis: Taurine therapy of nephropathic cystinosis may correct the deficiencies of cysteamine therapy.Molecular genetics and metabolism reports · 2025Article
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Targeting oxidative stress-induced lipid peroxidation enhances podocyte function in cystinosis.Journal of translational medicine · 2025Article
- Cystinosin is involved in NabioRxiv : the preprint server for biology · 2025Article
- Utilizing AI for the Identification and Validation of Novel Therapeutic Targets and Repurposed Drugs for Endometriosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation is critical for cell fate decisions, but the signals involved remain unclear. The kidney proximal tubule (PT) cells reabsorb disulphide-rich proteins through endocytosis, generating cystine via lysosomal proteolysis. Here we report that defective cystine mobilization from lysosomes through cystinosin (CTNS), which is mutated in cystinosis, diverts PT cells towards growth and proliferation, disrupting their functions. Mechanistically, cystine storage stimulates Ragulator-Rag GTPase-dependent recruitment of mechanistic target of rapamycin complex 1 (mTORC1) and its constitutive activation. Re-introduction of CTNS restores nutrient-dependent regulation of mTORC1 in knockout cells, whereas cell-permeant analogues of L-cystine, accumulating within lysosomes, render wild-type cells resistant to nutrient withdrawal. Therapeutic mTORC1 inhibition corrects lysosome and differentiation downstream of cystine storage, and phenotypes in preclinical models of cystinosis. Thus, cystine serves as a lysosomal signal that tailors mTORC1 and metabolism to direct epithelial cell fate decisions. These results identify mechanisms and therapeutic targets for dysregulated homeostasis in cystinosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.