Secretory autophagy maintains proteostasis upon lysosome inhibition.

Autor:	Solvik TA; Department of Pathology, University of California, San Francisco, San Francisco, CA.; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA., Nguyen TA; Department of Pathology, University of California, San Francisco, San Francisco, CA., Tony Lin YH; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA., Marsh T; Department of Pathology, University of California, San Francisco, San Francisco, CA.; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA., Huang EJ; Department of Pathology, University of California, San Francisco, San Francisco, CA., Wiita AP; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Debnath J; Department of Pathology, University of California, San Francisco, San Francisco, CA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA., Leidal AM; Department of Pathology, University of California, San Francisco, San Francisco, CA.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2022 Jun 06; Vol. 221 (6). Date of Electronic Publication: 2022 Apr 21.
DOI:	10.1083/jcb.202110151
Abstrakt:	The endolysosome system plays central roles in both autophagic degradation and secretory pathways, including the release of extracellular vesicles and particles (EVPs). Although previous work reveals important interconnections between autophagy and EVP-mediated secretion, our understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy pathway upregulated in response to endolysosomal inhibition, which mediates EVP-associated release of autophagic cargo receptors, including p62/SQSTM1. This secretion is highly regulated and dependent on multiple ATGs required for autophagosome formation, as well as the small GTPase Rab27a. Furthermore, disrupting autophagosome maturation, either via genetic inhibition of autophagosome-to-autolysosome fusion or expression of SARS-CoV-2 ORF3a, is sufficient to induce EVP secretion of autophagy cargo receptors. Finally, ATG-dependent EVP secretion buffers against the intracellular accumulation of autophagy cargo receptors when classical autophagic degradation is impaired. Thus, we propose secretory autophagy via EVPs functions as an alternate route to clear sequestered material and maintain proteostasis during endolysosomal dysfunction or impaired autophagosome maturation. (© 2022 Solvik et al.)
Databáze:	MEDLINE
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