TY - JOUR
T1 - Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo
AU - Dong, S.
AU - Aguirre-Hernandez, C.
AU - Scrivo, A.
AU - Eliscovich, C.
AU - Arias, E.
AU - Bravo-Cordero, J. J.
AU - Cuervo, A. M.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health AG021904, AG031782, AG038072, DK098408, NS100717 (to AMC); K22CA196750, Schneider-Lesser Foundation Award, TCI Young Scientist Cancer Research Award JJR Fund (P30-CA196521) (to JJBC), NIH/NIA AG038072 P&F, NIH/NIDDK DK041296 P&F (to EA) and NIH/NIDDK DK041296 Imaging and Cell Structure Core (to CE) and the generous support of the JPB Foundation, Rainwaters Foundation and Robert and Renée Belfer. We thank the Microscopy CoRE at Mount Sinai for technical support and Dr. Susmita Kaushik for critical reading of the manuscript.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Autophagy malfunctioning occurs in multiple human disorders, making attractive the idea of chemically modulating it with therapeutic purposes. However, for many types of autophagy, a clear understanding of tissue-specific differences in their activity and regulation is missing because of lack of methods to monitor these processes in vivo. Chaperone-mediated autophagy (CMA) is a selective type of autophagy that until now has only been studied in vitro and not in the tissue context at single cell resolution. Here, we develop a transgenic reporter mouse that allows dynamic measurement of CMA activity in vivo using image-based procedures. We identify previously unknown spatial and temporal differences in CMA activity in multiple organs and in response to stress. We illustrate the versatility of this model for monitoring CMA in live animals, organotypic cultures and cell cultures from these mice, and provide practical examples of multiorgan response to drugs that modulate CMA.
AB - Autophagy malfunctioning occurs in multiple human disorders, making attractive the idea of chemically modulating it with therapeutic purposes. However, for many types of autophagy, a clear understanding of tissue-specific differences in their activity and regulation is missing because of lack of methods to monitor these processes in vivo. Chaperone-mediated autophagy (CMA) is a selective type of autophagy that until now has only been studied in vitro and not in the tissue context at single cell resolution. Here, we develop a transgenic reporter mouse that allows dynamic measurement of CMA activity in vivo using image-based procedures. We identify previously unknown spatial and temporal differences in CMA activity in multiple organs and in response to stress. We illustrate the versatility of this model for monitoring CMA in live animals, organotypic cultures and cell cultures from these mice, and provide practical examples of multiorgan response to drugs that modulate CMA.
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U2 - 10.1038/s41467-019-14164-4
DO - 10.1038/s41467-019-14164-4
M3 - Article
C2 - 32005807
AN - SCOPUS:85078856265
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 645
ER -