ArticleCell reports2015
Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 2 of them syntheses that pooled it.
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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
238 citing papers in PubMed, 2 syntheses or guidelines pooled it, 353 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Astrocytic lactate shuttle disruption and the energy-starved lysosome in Alzheimer's disease.Research square · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Protein Modifications and Quality Control System: Target for Alzheimer's Disease Therapy.International journal of molecular sciences · 2026Review
- An alkaline nanosized platelet vesicle-based hydrogel for the treatment of osteoporotic bone defects.Materials today. Bio · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.bioRxiv : the preprint server for biology · 2026Article
- PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.American journal of physiology. Cell physiology · 2026Article
- Article
- Lysosomes as chemical and metabolic organizers of central nervous system injury and repair.Frontiers in chemistry · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Lysosomal pH Measurements via Dual-Imaging Microscopy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Exploratory Analysis of Autophagy-Lysosomal Pathway Proteins in Dermal Fibroblasts as Potential Peripheral Biomarkers for Alzheimer's Disease: A Pilot Study.Biomedicines · 2025Article
- C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity.Redox report : communications in free radical research · 2025Article
- The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases.Progress in neurobiology · 2025Review
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
178 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Presenilin 1 (PS1) deletion or Alzheimer's disease (AD)-linked mutations disrupt lysosomal acidification and proteolysis, which inhibits autophagy. Here, we establish that this phenotype stems from impaired glycosylation and instability of vATPase V0a1 subunit, causing deficient lysosomal vATPase assembly and function. We further demonstrate that elevated lysosomal pH in Presenilin 1 knockout (PS1KO) cells induces abnormal Ca(2+) efflux from lysosomes mediated by TRPML1 and elevates cytosolic Ca(2+). In WT cells, blocking vATPase activity or knockdown of either PS1 or the V0a1 subunit of vATPase reproduces all of these abnormalities. Normalizing lysosomal pH in PS1KO cells using acidic nanoparticles restores normal lysosomal proteolysis, autophagy, and Ca(2+) homeostasis, but correcting lysosomal Ca(2+) deficits alone neither re-acidifies lysosomes nor reverses proteolytic and autophagic deficits. Our results indicate that vATPase deficiency in PS1 loss-of-function states causes lysosomal/autophagy deficits and contributes to abnormal cellular Ca(2+) homeostasis, thus linking two AD-related pathogenic processes through a common molecular mechanism.
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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.