Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo

S. Dong, C. Aguirre-Hernandez, A. Scrivo, C. Eliscovich, E. Arias (), J. J. Bravo-Cordero () and A. M. Cuervo ()
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S. Dong: Department of Development and Molecular Biology, Albert Einstein College of Medicine
C. Aguirre-Hernandez: Department of Development and Molecular Biology, Albert Einstein College of Medicine
A. Scrivo: Department of Development and Molecular Biology, Albert Einstein College of Medicine
C. Eliscovich: Department of Medicine Marion Liver Research Center, Albert Einstein College of Medicine
E. Arias: Albert Einstein College of Medicine
J. J. Bravo-Cordero: Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
A. M. Cuervo: Department of Development and Molecular Biology, Albert Einstein College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14164-4

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