ArticleMolecular & cellular proteomics : MCP2017
Quantitative Proteome Analysis of Mouse Liver Lysosomes Provides Evidence for Mannose 6-phosphate-independent Targeting Mechanisms of Acid Hydrolases in Mucolipidosis II.
Article in Molecular & cellular proteomics : MCP, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Benchmarking Lysosome Enrichment Methods: A Guide for Research and Clinical Translation.Analytical chemistry · 2026Article
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- A multi-omics-empowered framework for precision diagnosis and treatment of lysosomal diseases.Journal of pharmaceutical analysis · 2025Review
- Article
- GOLPH3 and GOLPH3L maintain Golgi localization of LYSET and a functional mannose 6-phosphate transport pathway.The EMBO journal · 2024Article
- Starvation-induced metabolic rewiring affects mTORC1 composition in vivo.Scientific reports · 2024Article
- MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.Nature cell biology · 2024Article
- Dysregulated lysosomal exocytosis drives protease-mediated cartilage pathogenesis in multiple lysosomal disorders.iScience · 2024Article
- Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.eLife · 2024Article
- Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation.Nucleic acids research · 2024Article
- The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.Nature metabolism · 2022Article
- AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network.Molecular biology of the cell · 2022Article
- Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders.Molecular omics · 2022Review
- Autophagy in cancer cell remodeling and quality control.Molecular cell · 2022Review
- CREG1 promotes lysosomal biogenesis and function.Autophagy · 2021Article
- Dysregulation of mannose-6-phosphate-dependent cholesterol homeostasis in acinar cells mediates pancreatitis.The Journal of clinical investigation · 2021Article
- Review
- Recent Advances in Glycoproteomic Analysis by Mass Spectrometry.Analytical chemistry · 2020Review
- Article
- The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.Nature communications · 2019Article
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in misrouting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were identified that illustrated quantitative changes using an ion mobility-assisted data-independent label-free LC-MS approach. After validation of various differentially expressed lysosomal components by Western blotting and enzyme activity assays, the data revealed a small number of lysosomal proteins depending on M6P, including neuraminidase 1, cathepsin F, Npc2, and cathepsin L, whereas the majority reach lysosomes by alternative pathways. These data were compared with findings on cultured hepatocytes and liver sinusoid endothelial cells isolated from the liver of wild-type and PT-defective mice. Our findings show that the relative expression, targeting efficiency and lysosomal localization of lysosomal proteins tested in cultured hepatic cells resemble their proportion in isolated liver lysosomes. Hypersecretion of newly synthesized nonphosphorylated lysosomal proteins suggest that secretion-recapture mechanisms contribute to maintain major lysosomal functions in liver.
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