ArticleMolecular biology of the cell2015
A LAPF/phafin1-like protein regulates TORC1 and lysosomal membrane permeabilization in response to endoplasmic reticulum membrane stress.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- LAPF enhances lysosomal acidification to promote TLR9 and cGAS-STING-mediated antiviral immunity and attenuate HSV-1-induced neuroinflammatory pain.Journal of neuroinflammation · 2026Article
- The A2357T substitution in the kinase domain of yeast Tor1 confers growth promoting TORC1 activity independent of Gtr1/2 and Pib2.Scientific reports · 2026Article
- Multilayered regulation of TORC1 signaling by Ait1, Gcn2, and SEAC/GATOR during nitrogen limitation and starvation.Nature communications · 2025Article
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- Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans.Nature communications · 2024Article
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- The role of Phafin proteins in cell signaling pathways and diseases.Open life sciences · 2024Review
- Programmed Cell Death in Unicellular Versus Multicellular Organisms.Annual review of genetics · 2023Review
- Phafins Are More Than Phosphoinositide-Binding Proteins.International journal of molecular sciences · 2023Review
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- Conserved Pib2 regions have distinct roles in TORC1 regulation at the vacuole.Journal of cell science · 2022Article
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- ThemBio · 2022Article
- Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization.Cell reports · 2022Article
- Low-level lysosomal membrane permeabilization for limited release and sublethal functions of cathepsin proteases in the cytosol and nucleus.FEBS open bio · 2022Review
- Pib2 as an Emerging Master Regulator of Yeast TORC1.Biomolecules · 2021Review
- A glutamine sensor that directly activates TORC1.Communications biology · 2021Article
- Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomal membrane permeabilization (LMP) is a poorly understood regulator of programmed cell death that involves leakage of luminal lysosomal or vacuolar hydrolases into the cytoplasm. In Saccharomyces cerevisiae, LMP can be induced by antifungals and endoplasmic reticulum stressors when calcineurin also has been inactivated. A genome-wide screen revealed Pib2, a relative of LAPF/phafin1 that regulates LMP in mammals, as a pro-LMP protein in yeast. Pib2 associated with vacuolar and endosomal limiting membranes in unstressed cells in a manner that depended on its FYVE domain and on phosphatidylinositol 3-phosphate (PI(3)P) biosynthesis. Genetic experiments suggest that Pib2 stimulates the activity of TORC1, a vacuole-associated protein kinase that is sensitive to rapamycin, in a pathway parallel to the Ragulator/EGO complex containing the GTPases Gtr1 and Gtr2. A hyperactivating mutation in the catalytic subunit of TORC1 restored LMP to the gtr1∆ and pib2∆ mutants and also prevented the synthetic lethality of the double mutants. These findings show novel roles of PI(3)P and Pib2 in the regulation of TORC1, which in turn promoted LMP and nonapoptotic death of stressed cells. Rapamycin prevented the death of the pathogenic yeast Candida albicans during exposure to fluconazole plus a calcineurin inhibitor, suggesting that TORC1 broadly promotes sensitivity to fungistats in yeasts.
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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.