ArticleThe Journal of biological chemistry2015
The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- Cell cycle-linked vacuolar pH dynamics regulate amino acid homeostasis and cell growth.Nature metabolism · 2023Article
- Nuclear and cytoplasmic spatial protein quality control is coordinated by nuclear-vacuolar junctions and perinuclear ESCRT.Nature cell biology · 2023Article
- The vacuolar morphology protein VAC14 plays an important role in sexual development in the filamentous ascomycete Sordaria macrospora.Current genetics · 2022Article
- Article
- Acetate and hypertonic stress stimulate vacuole membrane fission using distinct mechanisms.PloS one · 2022Article
- Better Together: Current Insights Into Phagosome-Lysosome Fusion.Frontiers in immunology · 2021Review
- Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.Journal of inherited metabolic disease · 2020Article
- Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids.Frontiers in cell and developmental biology · 2020Review
- Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.Molecular neurobiology · 2019Article
- PIKfyve Deficiency in Myeloid Cells Impairs Lysosomal Homeostasis in Macrophages and Promotes Systemic Inflammation in Mice.Molecular and cellular biology · 2019Article
- Article
- Interaction of the late endo-lysosomal lipid PI(3,5)P2 with the Vph1 isoform of yeast V-ATPase increases its activity and cellular stress tolerance.The Journal of biological chemistry · 2019Article
- The PIKfyve complex regulates the early melanosome homeostasis required for physiological amyloid formation.Journal of cell science · 2019Article
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection.PLoS pathogens · 2019Article
- PI(3,5)PMolecular biology of the cell · 2018Article
- Article
- Article
- Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging inGenetics · 2017Article
- Early protection to stress mediated by CDK-dependent PI3,5PThe Journal of cell biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomes and the yeast vacuole are degradative and acidic organelles. Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a master architect of endolysosome and vacuole identity, is thought to be necessary for vacuolar acidification in yeast. There is also evidence that PtdIns(3,5)P2 may play a role in lysosomal acidification in higher eukaryotes. Nevertheless, these conclusions rely on qualitative assays of lysosome/vacuole pH. For example, quinacrine, an acidotropic fluorescent base, does not accumulate in the vacuoles of fab1Δ yeast. Fab1, along with its mammalian ortholog PIKfyve, is the lipid kinase responsible for synthesizing PtdIns(3,5)P2. In this study, we employed several assays that quantitatively assessed the lysosomal and vacuolar pH in PtdIns(3,5)P2-depleted cells. Using ratiometric imaging, we conclude that lysosomes retain a pH < 5 in PIKfyve-inhibited mammalian cells. In addition, quantitative fluorescence microscopy of vacuole-targeted pHluorin, a pH-sensitive GFP variant, indicates that fab1Δ vacuoles are as acidic as wild-type yeast. Importantly, we also employed fluorimetry of vacuoles loaded with cDCFDA, a pH-sensitive dye, to show that both wild-type and fab1Δ vacuoles have a pH < 5.0. In comparison, the vacuolar pH of the V-ATPase mutant vph1Δ or vph1Δ fab1Δ double mutant was 6.1. Although the steady-state vacuolar pH is not affected by PtdIns(3,5)P2 depletion, it may have a role in stabilizing the vacuolar pH during salt shock. Overall, we propose a model in which PtdIns(3,5)P2 does not govern the steady-state pH of vacuoles or lysosomes.
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