2025-12-23 スイス連邦工科大学ローザンヌ校(EPFL)
<関連情報>
- https://actu.epfl.ch/news/how-cells-balance-their-protein-levels/
- https://www.cell.com/cell-systems/fulltext/S2405-4712(25)00289-3
中核となる受動的および通性的なmTOR媒介メカニズムは、哺乳類のタンパク質合成と分解を調整する Core passive and facultative mTOR-mediated mechanisms coordinate mammalian protein synthesis and decay
Michael Shoujie Sun ∙ Benjamin Martin ∙ Joanna Dembska ∙ Ekaterina Lyublinskaya ∙ Cédric Deluz ∙ David M. Suter
Cell Systems Published:December 22, 2025
DOI:https://doi.org/10.1016/j.cels.2025.101456
Graphical abstract
Highlights
- Proteome-wide decay rates adapt to global changes in protein synthesis rate
- A passive mechanism is sufficient to explain this adaptation in most cell types
- An additional mTOR-driven mechanism allows for near-perfect adaptation in naive ES cells
- Divergent adaptation of degradation and dilution rates leads to proteome imbalance
Summary
The maintenance of cellular homeostasis requires tight regulation of proteome concentration and composition. To achieve this, protein production and elimination must be robustly coordinated. However, the mechanistic basis of this coordination remains unclear. Here, we address this question using quantitative live-cell imaging, computational modeling, transcriptomics, and proteomics approaches. We found that protein decay rates systematically adapt to global alterations of protein synthesis rates. This adaptation is driven by a core passive mechanism supplemented by facultative changes in mechanistic/mammalian target of rapamycin (mTOR) signaling. Passive adaptation hinges on changes in the production rate of the machinery governing protein decay and allows for partial maintenance of the cellular proteome. Sustained changes in mTOR signaling provide an additional layer of adaptation unique to naive pluripotent stem cells, allowing for near-perfect maintenance of proteome composition. Our work unravels the mechanisms protecting the integrity of mammalian proteomes upon variations in protein synthesis rates. A record of this paper’s transparent peer review process is included in the supplemental information.
