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PreprintCited by 37Autophagy in Disease and TherapyGenetics, Aging, and Longevity in Model OrganismsCellular transport and secretion

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Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity

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Yu, Yong, Gao, Shihong M., Guan, Youchen, Hu, Pei-Wen, Zhang, Qinghao, Liu, Jiaming, Jing, Bentian, Zhao, Qian, Sabatini, David M, Abu-Remaileh, Monther, Jung, Sung Yun, Wang, Meng C.·2022·eLife
DOI 10.1101/2022.10.16.512400PMC PMC10876212

Preprint — published as 10.7554/elife.85214 · Paper page

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Abstract

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with different longevity mechanisms. We further discovered the lysosomal recruitment of AMPK and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we discovered lysosomal heterogeneity across tissues as well as the specific enrichment of the Ragulator complex on Cystinosin positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity at different levels and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk and organism longevity.

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Metadata

Authors
Yu, Y., Gao, S. M., Guan, Y., Hu, P.-W., Zhang, Q., Liu, J., Jing, B., Zhao, Q., Sabatini, D. M., Abu-Remaileh, M., Jung, S. Y., & Wang, M. C.
Affiliations
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
  • Xiamen University (CN)
  • Stanford University (US)
Corresponding author
  • Yu, Yong
  • Wang, Meng C.
ORCID
Venue
eLife
Publisher
openRxiv
Published
2022-10-17
Volume
13
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2022.10.16.512400
PMC
PMC10876212
OpenAlex
W4391025916
Cited by
37
References
1
Citations by year
2026: 16 · 2025: 13 · 2024: 7 · 2023: 1
FWCI
10.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Howard Hughes Medical Institute
  • National Natural Science Foundation of China (32071146, P40OD010440)
  • National Institutes of Health (OD010440, P40OD010440)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
lysosomes, lysosomal proteome, longevity, AMPK, nucleoporins, Ragulator complex, cystinosin, lysosomal signaling, lysosomal metabolism, organelle crosstalk
MeSH terms
Intracellular Membranes, Lysosomes, Signal Transduction, Proteome, Proteomics

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