The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress

Abstract Autophagy is an evolutionarily conserved process that degrades cellular components to restore energy homeostasis under limited nutrient conditions. How this starvation-induced autophagy is regulated at the whole-body level is not fully understood. Here, we show that the tumor suppressor Lkb...

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Autores principales:	Laurie A. Mans, Laia Querol Cano, Jason van Pelt, Panagiota Giardoglou, Willem-Jan Keune, Anna-Pavlina G. Haramis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9bb0a73063543c0bfdc9ea6d0b08b78
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spelling	oai:doaj.org-article:a9bb0a73063543c0bfdc9ea6d0b08b782021-12-02T16:07:50ZThe tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress10.1038/s41598-017-07116-92045-2322https://doaj.org/article/a9bb0a73063543c0bfdc9ea6d0b08b782017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07116-9https://doaj.org/toc/2045-2322Abstract Autophagy is an evolutionarily conserved process that degrades cellular components to restore energy homeostasis under limited nutrient conditions. How this starvation-induced autophagy is regulated at the whole-body level is not fully understood. Here, we show that the tumor suppressor Lkb1, which activates the key energy sensor AMPK, also regulates starvation-induced autophagy at the organismal level. Lkb1-deficient zebrafish larvae fail to activate autophagy in response to nutrient restriction upon yolk termination, shown by reduced levels of the autophagy-activating proteins Atg5, Lc3-II and Becn1, and aberrant accumulation of the cargo receptor and autophagy substrate p62. We demonstrate that the autophagy defect in lkb1 mutants can be partially rescued by inhibiting mTOR signaling but not by inhibiting the PI3K pathway. Interestingly, mTOR-independent activation of autophagy restores degradation of the aberrantly accumulated p62 in lkb1 mutants and prolongs their survival. Our data uncover a novel critical role for Lkb1 in regulating starvation-induced autophagy at the organismal level, providing mechanistic insight into metabolic adaptation during development.Laurie A. MansLaia Querol CanoJason van PeltPanagiota GiardoglouWillem-Jan KeuneAnna-Pavlina G. HaramisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laurie A. Mans Laia Querol Cano Jason van Pelt Panagiota Giardoglou Willem-Jan Keune Anna-Pavlina G. Haramis The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
description	Abstract Autophagy is an evolutionarily conserved process that degrades cellular components to restore energy homeostasis under limited nutrient conditions. How this starvation-induced autophagy is regulated at the whole-body level is not fully understood. Here, we show that the tumor suppressor Lkb1, which activates the key energy sensor AMPK, also regulates starvation-induced autophagy at the organismal level. Lkb1-deficient zebrafish larvae fail to activate autophagy in response to nutrient restriction upon yolk termination, shown by reduced levels of the autophagy-activating proteins Atg5, Lc3-II and Becn1, and aberrant accumulation of the cargo receptor and autophagy substrate p62. We demonstrate that the autophagy defect in lkb1 mutants can be partially rescued by inhibiting mTOR signaling but not by inhibiting the PI3K pathway. Interestingly, mTOR-independent activation of autophagy restores degradation of the aberrantly accumulated p62 in lkb1 mutants and prolongs their survival. Our data uncover a novel critical role for Lkb1 in regulating starvation-induced autophagy at the organismal level, providing mechanistic insight into metabolic adaptation during development.
format	article
author	Laurie A. Mans Laia Querol Cano Jason van Pelt Panagiota Giardoglou Willem-Jan Keune Anna-Pavlina G. Haramis
author_facet	Laurie A. Mans Laia Querol Cano Jason van Pelt Panagiota Giardoglou Willem-Jan Keune Anna-Pavlina G. Haramis
author_sort	Laurie A. Mans
title	The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
title_short	The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
title_full	The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
title_fullStr	The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
title_full_unstemmed	The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress
title_sort	tumor suppressor lkb1 regulates starvation-induced autophagy under systemic metabolic stress
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a9bb0a73063543c0bfdc9ea6d0b08b78
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The tumor suppressor LKB1 regulates starvation-induced autophagy under systemic metabolic stress

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