Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.

0583525 - ÚOCHB 2025 RIV GB eng J - Journal Article
Yu, Y. - Gao, S. M. - Guan, Y. - Hu, P. W. - Zhang, Q. - Liu, J. - Jing, B. - Zhao, Q. - Sabatini, David M. - Abu-Remaileh, M. - Jung, S. Y. - Wang, M. C.
Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.
eLife. Roč. 13, January (2024). ISSN 2050-084X. E-ISSN 2050-084X
Institutional support: RVO:61388963
Impact factor: 7.7, year: 2022
Method of publishing: Open access
https://doi.org/10.7554/eLife.85214

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 four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase 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 further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity.
Permanent Link: https://hdl.handle.net/11104/0351543