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The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension
Human WIPI β-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn pro...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449903/ https://www.ncbi.nlm.nih.gov/pubmed/37620393 http://dx.doi.org/10.1038/s42003-023-05236-9 |
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author | Sporbeck, Katharina Haas, Maximilian L. Pastor-Maldonado, Carmen J. Schüssele, David S. Hunter, Catherine Takacs, Zsuzsanna Diogo de Oliveira, Ana L. Franz-Wachtel, Mirita Charsou, Chara Pfisterer, Simon G. Gubas, Andrea Haller, Patricia K. Knorr, Roland L. Kaulich, Manuel Macek, Boris Eskelinen, Eeva-Liisa Simonsen, Anne Proikas-Cezanne, Tassula |
author_facet | Sporbeck, Katharina Haas, Maximilian L. Pastor-Maldonado, Carmen J. Schüssele, David S. Hunter, Catherine Takacs, Zsuzsanna Diogo de Oliveira, Ana L. Franz-Wachtel, Mirita Charsou, Chara Pfisterer, Simon G. Gubas, Andrea Haller, Patricia K. Knorr, Roland L. Kaulich, Manuel Macek, Boris Eskelinen, Eeva-Liisa Simonsen, Anne Proikas-Cezanne, Tassula |
author_sort | Sporbeck, Katharina |
collection | PubMed |
description | Human WIPI β-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan. |
format | Online Article Text |
id | pubmed-10449903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104499032023-08-26 The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension Sporbeck, Katharina Haas, Maximilian L. Pastor-Maldonado, Carmen J. Schüssele, David S. Hunter, Catherine Takacs, Zsuzsanna Diogo de Oliveira, Ana L. Franz-Wachtel, Mirita Charsou, Chara Pfisterer, Simon G. Gubas, Andrea Haller, Patricia K. Knorr, Roland L. Kaulich, Manuel Macek, Boris Eskelinen, Eeva-Liisa Simonsen, Anne Proikas-Cezanne, Tassula Commun Biol Article Human WIPI β-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan. Nature Publishing Group UK 2023-08-24 /pmc/articles/PMC10449903/ /pubmed/37620393 http://dx.doi.org/10.1038/s42003-023-05236-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sporbeck, Katharina Haas, Maximilian L. Pastor-Maldonado, Carmen J. Schüssele, David S. Hunter, Catherine Takacs, Zsuzsanna Diogo de Oliveira, Ana L. Franz-Wachtel, Mirita Charsou, Chara Pfisterer, Simon G. Gubas, Andrea Haller, Patricia K. Knorr, Roland L. Kaulich, Manuel Macek, Boris Eskelinen, Eeva-Liisa Simonsen, Anne Proikas-Cezanne, Tassula The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title | The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title_full | The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title_fullStr | The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title_full_unstemmed | The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title_short | The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension |
title_sort | abl-myc axis controls wipi1-enhanced autophagy in lifespan extension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449903/ https://www.ncbi.nlm.nih.gov/pubmed/37620393 http://dx.doi.org/10.1038/s42003-023-05236-9 |
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