ArticleThe Journal of cell biology2020
Coupling APEX labeling to imaging mass spectrometry of single organelles reveals heterogeneity in lysosomal protein turnover.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4.bioRxiv : the preprint server for biology · 2026Article
- Recent Advances in Proximity Labeling-Based Subcellular Proteomic Mapping.Molecular & cellular proteomics : MCP · 2026Review
- Progress in monitoring molecular, cellular and metabolic dynamics using mass spectrometry imaging.Bioanalysis · 2025Review
- Nanoscale imaging of DNA-RNA identifies transcriptional plasticity at heterochromatin.Life science alliance · 2024Article
- Viewing Pulmonary Arterial Hypertension Pathogenesis and Opportunities for Disease-Modifying Therapy Through the Lens of Biomass.JACC. Basic to translational science · 2024Review
- Imaging plant metabolism in situ.Journal of experimental botany · 2024Review
- Subcellular protein turnover in human neural progenitor cells revealed by correlative electron microscopy and nanoscale secondary ion mass spectrometry imaging.Chemical science · 2024Article
- Spatially resolved mapping of proteome turnover dynamics with subcellular precision.Nature communications · 2023Article
- Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension.JCI insight · 2023Article
- Determining and interpreting protein lifetimes in mammalian tissues.Trends in biochemical sciences · 2023Review
- A Reliable Approach for Revealing Molecular Targets in Secondary Ion Mass Spectrometry.International journal of molecular sciences · 2022Article
- Article
- Functions of Stress-Induced Lipid Droplets in the Nervous System.Frontiers in cell and developmental biology · 2022Review
- Processing of progranulin into granulins involves multiple lysosomal proteases and is affected in frontotemporal lobar degeneration.Molecular neurodegeneration · 2021Article
- Novel technical developments in mass spectrometry imaging in 2020: A mini review.Analytical science advances · 2021Review
- Use of stable isotope-tagged thymidine and multi-isotope imaging mass spectrometry (MIMS) for quantification of human cardiomyocyte division.Nature protocols · 2021Article
- Metabolic Analysis at the Nanoscale with Multi-Isotope Imaging Mass Spectrometry (MIMS).Current protocols in cell biology · 2020Article
- Article
- Discovery of small molecules that normalize the transcriptome and enhance cysteine cathepsin activity in progranulin-deficient microglia.Scientific reports · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Quantification of stable isotope tracers after metabolic labeling provides a snapshot of the dynamic state of living cells and tissue. A form of imaging mass spectrometry quantifies isotope ratios with a lateral resolution <50 nm, using a methodology that we refer to as multi-isotope imaging mass spectrometry (MIMS). Despite lateral resolution exceeding diffraction-limited light microscopy, lack of contrast has largely limited use of MIMS to large or specialized subcellular structures, such as the nucleus and stereocilia. In this study, we repurpose the engineered peroxidase APEX2 as the first genetically encoded marker for MIMS. Coupling APEX2 labeling of lysosomes and metabolic labeling of protein, we identify that individual lysosomes exhibit substantial heterogeneity in protein age, which is lost in iPSC-derived neurons lacking the lysosomal protein progranulin. This study expands the practical use of MIMS for cell biology by enabling measurements of metabolic function from stable isotope labeling within individual organelles in situ.
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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.