ArticleThe Journal of clinical investigation2019
mTORC1 feedback to AKT modulates lysosomal biogenesis through MiT/TFE regulation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- AKT (Ser473) suppression mediates ceritinib cardiotoxicity through autophagic flux impairment and mitochondrial injury.Acta pharmacologica Sinica · 2026Article
- Postoperative management challenges in concurrent endometrioid carcinoma and PEComa a case report.Discover oncology · 2026Article
- TSC-associated microglial hyperactivity: enhanced calcium signaling, metabolism, and phagocytosis.Acta neuropathologica · 2026Article
- Wnt/β-Catenin-mTOR-autophagy crosstalk in breast cancer: context-dependent control of tumor progression, immune suppression, and therapeutic resistance.Frontiers in immunology · 2026Review
- SFPQ-TFE3 reciprocally regulates mTORC1 and induces lineage plasticity in a mouse model of renal tumorigenesis.Nature communications · 2025Article
- Loss of FMRP in microglia promotes degeneration of parvalbumin neurons and audiogenic seizures via progranulin insufficiency.bioRxiv : the preprint server for biology · 2025Article
- The role and mechanism of TSC in kidney diseases: a literature review.BMC nephrology · 2025Review
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Lysosomes: guardians and healers within cells- multifaceted perspective and outlook from injury repair to disease treatment.Cancer cell international · 2025Review
- Lysine-arginine imbalance overcomes therapeutic tolerance governed by the transcription factor E3-lysosome axis in glioblastoma.Nature communications · 2025Article
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Renal epithelioid angiomyolipomas overexpress TFE3 and the TFE3-regulated gene TRIM63 in the absence of TFE3 rearrangement.Virchows Archiv : an international journal of pathology · 2024Article
- Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.Scientific reports · 2024Article
- Aberrant monocytopoiesis drives granuloma development in sarcoidosis.International immunology · 2024Article
- Role of autophagy in angiogenic potential of vascular pericytes.Frontiers in cell and developmental biology · 2024Review
- The mitochondrial CabioRxiv : the preprint server for biology · 2023Article
- The mitochondrial CaFrontiers in cell and developmental biology · 2023Article
- An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss.Nature communications · 2022Article
- AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1.Nature communications · 2022Article
- Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The microphthalmia family of transcription factors (MiT/TFEs) controls lysosomal biogenesis and is negatively regulated by the nutrient sensor mTORC1. However, the mechanisms by which cells with constitutive mTORC1 signaling maintain lysosomal catabolism remain to be elucidated. Using the murine epidermis as a model system, we found that epidermal Tsc1 deletion resulted in a phenotype characterized by wavy hair and curly whiskers, and was associated with increased EGFR and HER2 degradation. Unexpectedly, constitutive mTORC1 activation with Tsc1 loss increased lysosomal content via upregulated expression and activity of MiT/TFEs, whereas genetic deletion of Rheb or Rptor or prolonged pharmacologic mTORC1 inactivation had the reverse effect. This paradoxical increase in lysosomal biogenesis by mTORC1 was mediated by feedback inhibition of AKT, and a resulting suppression of AKT-induced MiT/TFE downregulation. Thus, inhibiting hyperactive AKT signaling in the context of mTORC1 loss-of-function fully restored MiT/TFE expression and activity. These data suggest that signaling feedback loops work to restrain or maintain cellular lysosomal content during chronically inhibited or constitutively active mTORC1 signaling, respectively, and reveal a mechanism by which mTORC1 regulates upstream receptor tyrosine kinase signaling.
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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.