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Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo
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 met...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994528/ https://www.ncbi.nlm.nih.gov/pubmed/32005807 http://dx.doi.org/10.1038/s41467-019-14164-4 |
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author | Dong, S. Aguirre-Hernandez, C. Scrivo, A. Eliscovich, C. Arias, E. Bravo-Cordero, J. J. Cuervo, A. M. |
author_facet | Dong, S. Aguirre-Hernandez, C. Scrivo, A. Eliscovich, C. Arias, E. Bravo-Cordero, J. J. Cuervo, A. M. |
author_sort | Dong, S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6994528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69945282020-02-03 Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo Dong, S. Aguirre-Hernandez, C. Scrivo, A. Eliscovich, C. Arias, E. Bravo-Cordero, J. J. Cuervo, A. M. Nat Commun Article 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. Nature Publishing Group UK 2020-01-31 /pmc/articles/PMC6994528/ /pubmed/32005807 http://dx.doi.org/10.1038/s41467-019-14164-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dong, S. Aguirre-Hernandez, C. Scrivo, A. Eliscovich, C. Arias, E. Bravo-Cordero, J. J. Cuervo, A. M. Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title | Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title_full | Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title_fullStr | Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title_full_unstemmed | Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title_short | Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
title_sort | monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994528/ https://www.ncbi.nlm.nih.gov/pubmed/32005807 http://dx.doi.org/10.1038/s41467-019-14164-4 |
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