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Cited by 26Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsMetabolomics and Mass Spectrometry Studies

Targeted Quantification of the Lysosomal Proteome in Complex Samples

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Mosen, Peter, Sanner, Anne, Singh, Jasjot, Winter, Dominic·2021·Proteomes
DOI 10.3390/proteomes9010004PMC PMC7931001
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Abstract

In eukaryotic cells, lysosomes play a crucial role in the breakdown of a variety of components ranging from small molecules to complex structures, ascertaining the continuous turnover of cellular building blocks. Furthermore, they act as a regulatory hub for metabolism, being crucially involved in the regulation of major signaling pathways. Currently, ~450 lysosomal proteins can be reproducibly identified in a single cell line by mass spectrometry, most of which are low-abundant, restricting their unbiased proteomic analysis to lysosome-enriched fractions. In the current study, we applied two strategies for the targeted investigation of the lysosomal proteome in complex samples: data-independent acquisition (DIA) and parallel reaction monitoring (PRM). Using a lysosome-enriched fraction, mouse embryonic fibroblast whole cell lysate, and mouse liver whole tissue lysate, we investigated the capabilities of DIA and PRM to investigate the lysosomal proteome. While both approaches identified and quantified lysosomal proteins in all sample types, and their data largely correlated, DIA identified on average more proteins, especially for lower complex samples and longer chromatographic gradients. For the highly complex tissue sample and shorter gradients, however, PRM delivered a better performance regarding both identification and quantification of lysosomal proteins. All data are available via ProteomeXchange with identifier PXDD023278.

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  • Of the 37 GNPTAB trans-CDS pQTLs detected in the collapsing model, 35 (95%) are lysosomal proteins, 18 of which have been associated with other LSDs.

    “Of the 37 GNPTAB trans-CDS pQTLs detected in the collapsing model, 35 (95%) are lysosomal proteins25,26, 18 of which have been associated with other LSDs (Supplementary Table 9).”

    From Rare variant associations with plasma protein levels in the UK Biobank (2023) · cites this paper as [26]

    Section 3.3 (PRM Assay Development; page unavailable) describes a reference list of 374 lysosomal proteins, supporting the use of this paper to identify proteins as lysosomal. Our copy does not identify the 35 GNPTAB-associated proteins or establish that 35 of the 37 pQTL proteins are on that list. The 18 LSD associations are attributed to the citing paper’s Supplementary Table 9, not to this source. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Mosen, P., Sanner, A., Singh, J., & Winter, D.
Affiliations
University of Bonn (DE)
Corresponding author
Winter, Dominic
ORCID
Venue
Proteomes
Publisher
MDPI AG
Published
2021-01-26
Volume
9
Issue
1
Pages
4
ISSN
2227-7382 (ISSN-L)
DOI
10.3390/proteomes9010004
PMC
PMC7931001
OpenAlex
W3123087441
Cited by
26
References
5
Citations by year
2026: 5 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 2
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Proteomes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft (FOR2625)
  • Studienstiftung des Deutschen Volkes (n/a)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
lysosomal proteome, lysosomal proteins, targeted proteomics, data-independent acquisition, parallel reaction monitoring, mouse embryonic fibroblasts, mouse liver, low-abundance proteins

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