Nanosensor-based monitoring of autophagy-associated lysosomal acidification in vivo.

Autor: Kim M; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chen C; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA.; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Yaari Z; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Frederiksen R; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Randall E; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wollowitz J; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA.; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cupo C; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wu X; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA., Shah J; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Worroll D; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lagenbacher RE; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA., Goerzen D; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA., Li YM; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA., An H; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medicine, Cornell University, New York, NY, USA., Wang Y; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.; Maryland NanoCenter, University of Maryland, College Park, MD, USA., Heller DA; Memorial Sloan Kettering Cancer Center, New York, NY, USA. hellerd@mskcc.org.; Weill Cornell Medicine, Cornell University, New York, NY, USA. hellerd@mskcc.org.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2023 Dec; Vol. 19 (12), pp. 1448-1457. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1038/s41589-023-01364-9
Abstrakt: 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 sp 3 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: