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Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy
Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910460/ https://www.ncbi.nlm.nih.gov/pubmed/36574691 http://dx.doi.org/10.1073/pnas.2215126120 |
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author | Yao, Weijing Li, Yixing Chen, Yingcong Chen, Yuting Zhao, Pengwei Zhang, Yi Jiang, Qiang Feng, Yuyao Yang, Fan Wu, Choufei Zhong, Huiming Zhou, Yiting Sun, Qiming Zhang, Liqin Liu, Wei Yi, Cong |
author_facet | Yao, Weijing Li, Yixing Chen, Yingcong Chen, Yuting Zhao, Pengwei Zhang, Yi Jiang, Qiang Feng, Yuyao Yang, Fan Wu, Choufei Zhong, Huiming Zhou, Yiting Sun, Qiming Zhang, Liqin Liu, Wei Yi, Cong |
author_sort | Yao, Weijing |
collection | PubMed |
description | Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13–Mec1 interaction revealed two previously unrecognized protein regions, the Mec1-Binding Region (MBR) on Atg13 and the Atg13-Binding Region (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS. |
format | Online Article Text |
id | pubmed-9910460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-99104602023-06-27 Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy Yao, Weijing Li, Yixing Chen, Yingcong Chen, Yuting Zhao, Pengwei Zhang, Yi Jiang, Qiang Feng, Yuyao Yang, Fan Wu, Choufei Zhong, Huiming Zhou, Yiting Sun, Qiming Zhang, Liqin Liu, Wei Yi, Cong Proc Natl Acad Sci U S A Biological Sciences Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13–Mec1 interaction revealed two previously unrecognized protein regions, the Mec1-Binding Region (MBR) on Atg13 and the Atg13-Binding Region (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS. National Academy of Sciences 2022-12-27 2023-01-03 /pmc/articles/PMC9910460/ /pubmed/36574691 http://dx.doi.org/10.1073/pnas.2215126120 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Yao, Weijing Li, Yixing Chen, Yingcong Chen, Yuting Zhao, Pengwei Zhang, Yi Jiang, Qiang Feng, Yuyao Yang, Fan Wu, Choufei Zhong, Huiming Zhou, Yiting Sun, Qiming Zhang, Liqin Liu, Wei Yi, Cong Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title | Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title_full | Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title_fullStr | Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title_full_unstemmed | Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title_short | Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy |
title_sort | mec1 regulates pas recruitment of atg13 via direct binding with atg13 during glucose starvation-induced autophagy |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910460/ https://www.ncbi.nlm.nih.gov/pubmed/36574691 http://dx.doi.org/10.1073/pnas.2215126120 |
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