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Publication : Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy.

First Author  Krause GJ Year  2023
Journal  Cell Rep Volume  42
Issue  12 Pages  113529
PubMed ID  38060380 Mgi Jnum  J:344300
Mgi Id  MGI:7574047 Doi  10.1016/j.celrep.2023.113529
Citation  Krause GJ, et al. (2023) Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy. Cell Rep 42(12):113529
abstractText  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.
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