Cai, Rong, Ren, Jiayu, Guo, Mengyu, Wei, Taotao, Liu, Ying, Xie, Chunyu, Zhang, Peng, Guo, Zhiling, Chetwynd, Andrew J 
ORCID: 0000-0001-6648-6881, Ke, Pu Chun et al (show 2 more authors)
(2022)
Dynamic intracellular exchange of nanomaterials' protein corona perturbs proteostasis and remodels cell metabolism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119 (23).
e2200363119-.
Abstract
The nanomaterial–protein “corona” is a dynamic entity providing a synthetic–natural interface mediating cellular uptake and subcellular distribution of nanomaterials in biological systems. As nanomaterials are central to the safe-by-design of future nanomedicines and the practice of nanosafety, understanding and delineating the biological and toxicological signatures of the ubiquitous nanomaterial–protein corona are precursors to the continued development of nano–bio science and engineering. However, despite well over a decade of extensive research, the dynamics of intracellular release or exchange of the blood protein corona from nanomaterials following their cellular internalization remains unclear, and the biological footprints of the nanoparticle–protein corona traversing cellular compartments are even less well understood. To address this crucial bottleneck, the current work screened evolution of the intracellular protein corona along the endocytotic pathway from blood via lysosomes to cytoplasm in cancer cells. Intercellular proteins, including pyruvate kinase M2 (PKM2), and chaperones, displaced some of the initially adsorbed blood proteins from the nanoparticle surface, which perturbed proteostasis and subsequently incited chaperone-mediated autophagy (CMA) to disrupt the key cellular metabolism pathway, including glycolysis and lipid metabolism. Since proteostasis is key to the sustainability of cell function, its collapse and the resulting CMA overdrive spell subsequent cell death and aging. Our findings shed light on the consequences of the transport of extracellular proteins by nanoparticles on cell metabolism.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cell metabolism, chaperone-mediated autophagy, protein corona, proteostasis |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 Oct 2023 09:28 |
| Last Modified: | 02 Oct 2023 09:29 |
| DOI: | 10.1073/pnas.2200363119 |
| Open Access URL: | https://doi.org/10.1073/pnas.2200363119 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173276 |
Dimensions
Dimensions
