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

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:42

Enthalten in:

Cell reports - 42(2023), 12 vom: 26. Dez., Seite 113529

Sprache:

Englisch

Beteiligte Personen:

Krause, Gregory J [VerfasserIn]
Kirchner, Philipp [VerfasserIn]
Stiller, Barbara [VerfasserIn]
Morozova, Kateryna [VerfasserIn]
Diaz, Antonio [VerfasserIn]
Chen, Kuei-Ho [VerfasserIn]
Krogan, Nevan J [VerfasserIn]
Agullo-Pascual, Esperanza [VerfasserIn]
Clement, Cristina C [VerfasserIn]
Lindenau, Kristen [VerfasserIn]
Swaney, Danielle L [VerfasserIn]
Dilipkumar, Shilpa [VerfasserIn]
Bravo-Cordero, Jose Javier [VerfasserIn]
Santambrogio, Laura [VerfasserIn]
Cuervo, Ana Maria [VerfasserIn]

Links:

Volltext

Themen:

Autophagy
Bag6
CP: Molecular biology
Chaperone
Journal Article
Late endosome
Lysosome
Microautophagy
Molecular Chaperones
Protein degradation
Protein targeting
Proteostasis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Starvation

Anmerkungen:

Date Completed 01.01.2024

Date Revised 10.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.celrep.2023.113529

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365512761