ArticleThe Journal of general physiology2013
A model of lysosomal pH regulation.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 188 citations in OpenAlex.
- Lysosome-Acidifying Nanoparticles Rescue A30P α-Synuclein Induced Neuronal Death in Cellular and Drosophila Models of Parkinson's Disease.Advanced healthcare materials · 2026Article
- Chromaffin Versus Platelet Granules: What We Have Learned From Chromaffin Cells for Human Studies.Journal of neurochemistry · 2026Review
- 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
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Dominant Action ofCells · 2025Article
- Functional analyses and integrated mechanisms of cellular destruction by L-amino acid oxidase.Cell death & disease · 2025Article
- Lysosomal and mTORC1 signaling dysregulation underpin the pathology of spastic paraplegia type 80.Nature communications · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Detection of Cytosolic Ion Concentrations by the Trans-Golgi Network/Early Endosome is Important for Salt Tolerance.bioRxiv : the preprint server for biology · 2025Article
- Quantitative modeling of rod outer segment phagocytosis and recycling.Scientific reports · 2025Article
- Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.bioRxiv : the preprint server for biology · 2025Article
- An Open-Science Computational Model of Organelle Acidification to Integrate Putative Mechanisms of Synaptic Vesicle Acidification and Filling.Neurochemical research · 2025Article
- Article
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- Membrane Transport Modulates the pH-Regulated Feedback of an Enzyme Reaction Confined within Lipid Vesicles.ACS nano · 2025Article
- Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson's disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation.NPJ Parkinson's disease · 2025Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.Molecular cancer research : MCR · 2024Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosomes must maintain an acidic luminal pH to activate hydrolytic enzymes and degrade internalized macromolecules. Acidification requires the vacuolar-type H(+)-ATPase to pump protons into the lumen and a counterion flux to neutralize the membrane potential created by proton accumulation. Early experiments suggested that the counterion was chloride, and more recently a pathway consistent with the ClC-7 Cl(-)/H(+) antiporter was identified. However, reports that the steady-state luminal pH is unaffected in ClC-7 knockout mice raise questions regarding the identity of the carrier and the counterion. Here, we measure the current-voltage characteristics of a mammalian ClC-7 antiporter, and we use its transport properties, together with other key ion regulating elements, to construct a mathematical model of lysosomal pH regulation. We show that results of in vitro lysosome experiments can only be explained by the presence of ClC-7, and that ClC-7 promotes greater acidification than Cl(-), K(+), or Na(+) channels. Our models predict strikingly different lysosomal K(+) dynamics depending on the major counterion pathways. However, given the lack of experimental data concerning acidification in vivo, the model cannot definitively rule out any given mechanism, but the model does provide concrete predictions for additional experiments that would clarify the identity of the counterion and its carrier.
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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.