Universität zu Köln

Kumsta, Caroline, Chang, Jessica T., Lee, Reina, Tan, Ee Phie, Yang, Yongzhi, Loureiro, Rute, Choy, Elizabeth H., Lim, Shaun H. Y., Saez, Isabel, Springhorn, Alexander, Hoppe, Thorsten ORCID: 0000-0002-4734-9352, Vilchez, David and Hansen, Malene (2019). The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Autophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates the degradation of ubiquitinated cargo. While the process of autophagy has been linked to aging, the impact of selective autophagy in lifespan regulation remains unclear. We have recently shown in Caenorhabditis elegans that transcript levels of sqst-1/p62 increase upon a hormetic heat shock, suggesting a role of SQST-1/p62 in stress response and aging. Here, we find that sqst-1/p62 is required for hormetic benefits of heat shock, including longevity, improved neuronal proteostasis, and autophagy induction. Furthermore, overexpression of SQST-1/p62 is sufficient to induce autophagy in distinct tissues, extend lifespan, and improve the fitness of mutants with defects in proteostasis in an autophagy-dependent manner. Collectively, these findings illustrate that increased expression of a selective autophagy receptor is sufficient to induce autophagy, enhance proteostasis and extend longevity, and demonstrate an important role for sqst-1/p62 in proteotoxic stress responses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kumsta, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Chang, Jessica T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Reina UNSPECIFIED UNSPECIFIED UNSPECIFIED Tan, Ee Phie UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Yongzhi UNSPECIFIED UNSPECIFIED UNSPECIFIED Loureiro, Rute UNSPECIFIED UNSPECIFIED UNSPECIFIED Choy, Elizabeth H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lim, Shaun H. Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saez, Isabel UNSPECIFIED UNSPECIFIED UNSPECIFIED Springhorn, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Vilchez, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Malene UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124559
DOI:	10.1038/s41467-019-13540-4
Journal or Publication Title:	Nat. Commun.
Volume:	10
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INCLUSION-BODY FORMATION; LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; MONITORING AUTOPHAGY; PROTEIN AGGREGATION; STRUCTURAL BASIS; P62; STRESS; GENES; ACCUMULATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12455