ArticleMolecular cell2023
Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 130 citations in OpenAlex.
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- A mycobacterial Sec61 inhibitor disrupts lysosome function by blocking Vacuolar-ATPase biosynthesis.European journal of cell biology · 2026Article
- Lysosomal Membrane Protein SCARB2 Mediates the Pathogenesis of Diabetic Retinopathy Through the MAPK/ERK/MMP9 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Entorhinal Astrocyte Transplants Restore Spatial Exploration and Alleviate Amyloid-Beta Pathology in Alzheimer's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ANGPTL4 Exacerbates Renal Injury in Diabetic Kidney Disease by Impairing Podocyte Lipophagy via Compromised Lysosomal Degradative Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Controlled assembly of exogenous DNA-based materials in living cells.Fundamental research · 2026Review
- Relevance of functional studies for assessing an antisense oligonucleotide-mediated exon skipping therapeutic strategy for mucolipidosis type II.Orphanet journal of rare diseases · 2026Article
- Targeting lysosomal pH restores mitochondrial quality control in GBA1-mutant Parkinson's disease.Translational neurodegeneration · 2026Article
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Enhancing platinum-based chemotherapy efficacy and safety through combination therapy-mediated remodeling of autophagic homeostasis in gastric cancer.Cell death & disease · 2026Article
- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Epigenetic Responses to Abusive versus Accidental Injuries in Children: A Cross-sectional Epigenome Wide Association Meta-analysis.medRxiv : the preprint server for health sciences · 2026Article
- Deficiency of lysosomal TMEM175 in myeloid macrophages exerts anti-tumor immunity via inflammasome and cross-presentation pathway.Nature communications · 2026Article
- A Chemoenzymatic Method To Systematically Quantify Core Fucosylation Stoichiometry of Glycoproteins and Reveal Its Roles in EMT and Embryonic Development.Analytical chemistry · 2026Article
- TMEM175 does not function as a proton-selective ion channel to prevent lysosomal over-acidification.The Journal of cell biology · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Maintaining a highly acidic lysosomal pH is central to cellular physiology. Here, we use functional proteomics, single-particle cryo-EM, electrophysiology, and in vivo imaging to unravel a key biological function of human lysosome-associated membrane proteins (LAMP-1 and LAMP-2) in regulating lysosomal pH homeostasis. Despite being widely used as a lysosomal marker, the physiological functions of the LAMP proteins have long been overlooked. We show that LAMP-1 and LAMP-2 directly interact with and inhibit the activity of the lysosomal cation channel TMEM175, a key player in lysosomal pH homeostasis implicated in Parkinson's disease. This LAMP inhibition mitigates the proton conduction of TMEM175 and facilitates lysosomal acidification to a lower pH environment crucial for optimal hydrolase activity. Disrupting the LAMP-TMEM175 interaction alkalinizes the lysosomal pH and compromises the lysosomal hydrolytic function. In light of the ever-increasing importance of lysosomes to cellular physiology and diseases, our data have widespread implications for lysosomal biology.
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Registered trials
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