ArticleJournal of cell science2018
Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 154 citations in OpenAlex.
- PI(3,5)PScience advances · 2026Article
- Quantitative comparison of PI(3,5)PMolecular biology of the cell · 2026Article
- Facile synthesis of amorphous coordinated metal-drug frameworks for cancer immunotherapy.Materials today. Bio · 2026Article
- VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair.Nature communications · 2026Article
- A PI(3,5)PNature communications · 2026Article
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
- PIKfyve is required for efficient phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes.Journal of cell science · 2026Article
- Obinutuzumab induces lysosomal destabilization via sphingomyelin-dependent inhibition of TRPML2.Scientific reports · 2026Article
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses.bioRxiv : the preprint server for biology · 2025Article
- Quantitative comparison of PI(3,5)PbioRxiv : the preprint server for biology · 2025Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- CRISPRi screening identifies PIKfyve as a co-therapeutic target for obinutuzumab.Clinical and translational medicine · 2025Article
- Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer.Cancer research · 2025Article
- Loss of SETD2 in wild-type VHL clear cell renal cell carcinoma sensitizes cells to STF-62247 and leads to DNA damage, cell cycle arrest, and cell death characteristic of pyroptosis.Molecular oncology · 2025Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects, including embryonic lethality, neurodegeneration and overt inflammation. The reasons for such drastic lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF, enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells.
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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.