Nanosensor-based monitoring of autophagy-associated lysosomal acidification in vivo Journal Article
| Authors: | Kim, M.; Chen, C.; Yaari, Z.; Frederiksen, R.; Randall, E.; Wollowitz, J.; Cupo, C.; Wu, X.; Shah, J.; Worroll, D.; Lagenbacher, R. E.; Goerzen, D.; Li, Y. M.; An, H.; Wang, Y. H.; Heller, D. A. |
| Article Title: | Nanosensor-based monitoring of autophagy-associated lysosomal acidification in vivo |
| Abstract: | Autophagy is a cellular process with important functions that drive neurodegenerative diseases and cancers. Lysosomal hyperacidification is a hallmark of autophagy. Lysosomal pH is currently measured by fluorescent probes in cell culture, but existing methods do not allow for quantitative, transient or in vivo measurements. In the present study, we developed near-infrared optical nanosensors using organic color centers (covalent sp3 defects on carbon nanotubes) to measure autophagy-mediated endolysosomal hyperacidification in live cells and in vivo. The nanosensors localize to the lysosomes, where the emission band shifts in response to local pH, enabling spatial, dynamic and quantitative mapping of subtle changes in lysosomal pH. Using the sensor, we observed cellular and intratumoral hyperacidification on administration of mTORC1 and V-ATPase modulators, revealing that lysosomal acidification mirrors the dynamics of S6K dephosphorylation and LC3B lipidation while diverging from p62 degradation. This sensor enables the transient and in vivo monitoring of the autophagy–lysosomal pathway. [Figure not available: see fulltext.]. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | s6 kinase; unclassified drug; nonhuman; comparative study; monitoring; animal cell; mouse; metabolism; protein degradation; animal experiment; protein; ph; in vivo study; physiology; quantitative analysis; autophagy; adenosine triphosphatase; oligonucleotide; optics; synthesis; hydrogen-ion concentration; lysosome; lysosomes; modulation; tumor microenvironment; dephosphorylation; infrared radiation; mammalian target of rapamycin complex 1; carbon nanotube; single walled nanotube; nanotubes, carbon; acidification; color; article; cells by body anatomy; hyperspectral imaging; autophagy (cellular); sequestosome 1; mechanistic target of rapamycin complex 1; protein lc3b; endolysosome; lysosomal ph |
| Journal Title: | Nature Chemical Biology |
| Volume: | 19 |
| Issue: | 12 |
| ISSN: | 1552-4450 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-12-01 |
| Start Page: | 1448 |
| End Page: | 1457 |
| Language: | English |
| DOI: | 10.1038/s41589-023-01364-9 |
| PUBMED: | 37322156 |
| PROVIDER: | scopus |
| PMCID: | PMC10721723 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Daniel Heller -- Source: Scopus |
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