Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for the chaperone protein Bag6 in triage and internalization of eMI substrates into late endosomes. Association and dynamics of Bag6 at the late endosome membrane change during starvation, a stressor that, contrary to other autophagic pathways, causes a decline in eMI activity. Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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Enthalten in: |
Cell reports - 42(2023), 12 vom: 26. Dez., Seite 113529 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Krause, Gregory J [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 01.01.2024 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.celrep.2023.113529 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM365512761 |
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520 | |a Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for the chaperone protein Bag6 in triage and internalization of eMI substrates into late endosomes. Association and dynamics of Bag6 at the late endosome membrane change during starvation, a stressor that, contrary to other autophagic pathways, causes a decline in eMI activity. Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them | ||
650 | 4 | |a Journal Article | |
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650 | 4 | |a Research Support, Non-U.S. Gov't | |
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650 | 4 | |a microautophagy | |
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650 | 4 | |a protein targeting | |
650 | 4 | |a proteostasis | |
650 | 4 | |a starvation | |
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700 | 1 | |a Kirchner, Philipp |e verfasserin |4 aut | |
700 | 1 | |a Stiller, Barbara |e verfasserin |4 aut | |
700 | 1 | |a Morozova, Kateryna |e verfasserin |4 aut | |
700 | 1 | |a Diaz, Antonio |e verfasserin |4 aut | |
700 | 1 | |a Chen, Kuei-Ho |e verfasserin |4 aut | |
700 | 1 | |a Krogan, Nevan J |e verfasserin |4 aut | |
700 | 1 | |a Agullo-Pascual, Esperanza |e verfasserin |4 aut | |
700 | 1 | |a Clement, Cristina C |e verfasserin |4 aut | |
700 | 1 | |a Lindenau, Kristen |e verfasserin |4 aut | |
700 | 1 | |a Swaney, Danielle L |e verfasserin |4 aut | |
700 | 1 | |a Dilipkumar, Shilpa |e verfasserin |4 aut | |
700 | 1 | |a Bravo-Cordero, Jose Javier |e verfasserin |4 aut | |
700 | 1 | |a Santambrogio, Laura |e verfasserin |4 aut | |
700 | 1 | |a Cuervo, Ana Maria |e verfasserin |4 aut | |
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