ArticleThe Journal of general physiology2016
Soluble adenylyl cyclase is essential for proper lysosomal acidification.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Targeting Soluble Adenylyl Cyclase for On-Demand Contraception.Physiology (Bethesda, Md.) · 2026Review
- Understanding Target-Specific Effects of Antidepressant Drug Pollution on Molluscs: A Systematic Review Report.Toxics · 2025Review
- cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.bioRxiv : the preprint server for biology · 2025Article
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- The role of soluble adenylyl cyclase in sensing and regulating intracellular pH.Pflugers Archiv : European journal of physiology · 2024Review
- The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction.Calcified tissue international · 2024Article
- Effect of Roflumilast, a Selective PDE4 Inhibitor, on Bone Phenotypes in ADO2 Mice.Calcified tissue international · 2024Article
- Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration.Journal of neuroinflammation · 2023Review
- Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases.Translational neurodegeneration · 2023Review
- Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.Cell reports · 2023Article
- Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.Journal of chemical information and modeling · 2023Article
- Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.Journal of medicinal chemistry · 2022Article
- Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes.Cell · 2022Article
- Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19.International journal of biological sciences · 2022Review
- Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential.Frontiers in physiology · 2022Article
- Strategies to safely target widely expressed soluble adenylyl cyclase for contraception.Frontiers in pharmacology · 2022Article
- Measurement of Melanin Metabolism in Live Cells by [U-The Journal of investigative dermatology · 2021Article
- Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase.Interface focus · 2021Review
- Regulation of Mitochondrial Homeostasis by sAC-Derived cAMP Pool: Basic and Translational Aspects.Cells · 2021Review
Corrections and comments
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Authors and funding
5 authors.
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Abstract
Lysosomes, the degradative organelles of the endocytic and autophagic pathways, function at an acidic pH. Lysosomes are acidified by the proton-pumping vacuolar ATPase (V-ATPase), but the molecular processes that set the organelle's pH are not completely understood. In particular, pH-sensitive signaling enzymes that can regulate lysosomal acidification in steady-state physiological conditions have yet to be identified. Soluble adenylyl cyclase (sAC) is a widely expressed source of cAMP that serves as a physiological pH sensor in cells. For example, in proton-secreting epithelial cells, sAC is responsible for pH-dependent translocation of V-ATPase to the luminal surface. Here we show genetically and pharmacologically that sAC is also essential for lysosomal acidification. In the absence of sAC, V-ATPase does not properly localize to lysosomes, lysosomes fail to fully acidify, lysosomal degradative capacity is diminished, and autophagolysosomes accumulate.
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