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The Hedgehog signalling pathway regulates autophagy

Autophagy is a highly conserved degradative process that removes damaged or unnecessary proteins and organelles, and recycles cytoplasmic contents during starvation. Autophagy is essential in physiological processes such as embryonic development but how autophagy is regulated by canonical developmen...

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Autores principales: Jimenez-Sanchez, Maria, Menzies, Fiona M., Chang, Yu-Yun, Simecek, Nikol, Neufeld, Thomas P., Rubinsztein, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514496/
https://www.ncbi.nlm.nih.gov/pubmed/23149744
http://dx.doi.org/10.1038/ncomms2212
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author Jimenez-Sanchez, Maria
Menzies, Fiona M.
Chang, Yu-Yun
Simecek, Nikol
Neufeld, Thomas P.
Rubinsztein, David C.
author_facet Jimenez-Sanchez, Maria
Menzies, Fiona M.
Chang, Yu-Yun
Simecek, Nikol
Neufeld, Thomas P.
Rubinsztein, David C.
author_sort Jimenez-Sanchez, Maria
collection PubMed
description Autophagy is a highly conserved degradative process that removes damaged or unnecessary proteins and organelles, and recycles cytoplasmic contents during starvation. Autophagy is essential in physiological processes such as embryonic development but how autophagy is regulated by canonical developmental pathways is unclear. Here we show that the Hedgehog signalling pathway inhibits autophagosome synthesis, both in basal and in autophagy-induced conditions. This mechanism is conserved in mammalian cells and in Drosophila, and requires the orthologous transcription factors Gli2 and Ci, respectively. Furthermore, we identify that activation of the Hedgehog pathway reduces PERK levels, concomitant with a decrease in phosphorylation of the translation initiation factor eukaryotic initiation factor 2α, suggesting a novel target of this pathway and providing a possible link between Hedgehog signalling and autophagy.
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spelling pubmed-35144962012-12-05 The Hedgehog signalling pathway regulates autophagy Jimenez-Sanchez, Maria Menzies, Fiona M. Chang, Yu-Yun Simecek, Nikol Neufeld, Thomas P. Rubinsztein, David C. Nat Commun Article Autophagy is a highly conserved degradative process that removes damaged or unnecessary proteins and organelles, and recycles cytoplasmic contents during starvation. Autophagy is essential in physiological processes such as embryonic development but how autophagy is regulated by canonical developmental pathways is unclear. Here we show that the Hedgehog signalling pathway inhibits autophagosome synthesis, both in basal and in autophagy-induced conditions. This mechanism is conserved in mammalian cells and in Drosophila, and requires the orthologous transcription factors Gli2 and Ci, respectively. Furthermore, we identify that activation of the Hedgehog pathway reduces PERK levels, concomitant with a decrease in phosphorylation of the translation initiation factor eukaryotic initiation factor 2α, suggesting a novel target of this pathway and providing a possible link between Hedgehog signalling and autophagy. Nature Pub. Group 2012-11-13 /pmc/articles/PMC3514496/ /pubmed/23149744 http://dx.doi.org/10.1038/ncomms2212 Text en Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Jimenez-Sanchez, Maria
Menzies, Fiona M.
Chang, Yu-Yun
Simecek, Nikol
Neufeld, Thomas P.
Rubinsztein, David C.
The Hedgehog signalling pathway regulates autophagy
title The Hedgehog signalling pathway regulates autophagy
title_full The Hedgehog signalling pathway regulates autophagy
title_fullStr The Hedgehog signalling pathway regulates autophagy
title_full_unstemmed The Hedgehog signalling pathway regulates autophagy
title_short The Hedgehog signalling pathway regulates autophagy
title_sort hedgehog signalling pathway regulates autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514496/
https://www.ncbi.nlm.nih.gov/pubmed/23149744
http://dx.doi.org/10.1038/ncomms2212
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