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ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3
UNC51-like kinase-1 (ULK1) is the catalytic component of the autophagy pre-initiation complex that stimulates autophagy via phosphorylation of ATG14, BECLN1 and other autophagy proteins. ULK1 has also been shown to specifically promote mitophagy but the mechanistic basis of how has remained unclear....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519931/ https://www.ncbi.nlm.nih.gov/pubmed/34654847 http://dx.doi.org/10.1038/s41598-021-00170-4 |
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author | Poole, Logan P. Bock-Hughes, Althea Berardi, Damian E. Macleod, Kay F. |
author_facet | Poole, Logan P. Bock-Hughes, Althea Berardi, Damian E. Macleod, Kay F. |
author_sort | Poole, Logan P. |
collection | PubMed |
description | UNC51-like kinase-1 (ULK1) is the catalytic component of the autophagy pre-initiation complex that stimulates autophagy via phosphorylation of ATG14, BECLN1 and other autophagy proteins. ULK1 has also been shown to specifically promote mitophagy but the mechanistic basis of how has remained unclear. Here we show that ULK1 phosphorylates the BNIP3 mitochondrial cargo receptor on a critical serine residue (S17) adjacent to its amino terminal LIR motif. ULK1 similarly phosphorylates BNIP3L on S35. Phosphorylation of BNIP3 on S17 by ULK1 promotes interaction with LC3 and mitophagy. ULK1 interaction also promotes BNIP3 protein stability by limiting its turnover at the proteasome. The ability of ULK1 to regulate BNIP3 protein stability depends on an intact “BH3” domain and deletion of its “BH3” domain reduces BNIP3 turnover and increases BNIP3 protein levels independent of ULK1. In summary ULK1 promotes mitophagy by both stabilization of BNIP3 protein and via phosphorylation of S17 to stimulate interaction with LC3. |
format | Online Article Text |
id | pubmed-8519931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85199312021-10-20 ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 Poole, Logan P. Bock-Hughes, Althea Berardi, Damian E. Macleod, Kay F. Sci Rep Article UNC51-like kinase-1 (ULK1) is the catalytic component of the autophagy pre-initiation complex that stimulates autophagy via phosphorylation of ATG14, BECLN1 and other autophagy proteins. ULK1 has also been shown to specifically promote mitophagy but the mechanistic basis of how has remained unclear. Here we show that ULK1 phosphorylates the BNIP3 mitochondrial cargo receptor on a critical serine residue (S17) adjacent to its amino terminal LIR motif. ULK1 similarly phosphorylates BNIP3L on S35. Phosphorylation of BNIP3 on S17 by ULK1 promotes interaction with LC3 and mitophagy. ULK1 interaction also promotes BNIP3 protein stability by limiting its turnover at the proteasome. The ability of ULK1 to regulate BNIP3 protein stability depends on an intact “BH3” domain and deletion of its “BH3” domain reduces BNIP3 turnover and increases BNIP3 protein levels independent of ULK1. In summary ULK1 promotes mitophagy by both stabilization of BNIP3 protein and via phosphorylation of S17 to stimulate interaction with LC3. Nature Publishing Group UK 2021-10-15 /pmc/articles/PMC8519931/ /pubmed/34654847 http://dx.doi.org/10.1038/s41598-021-00170-4 Text en © The Author(s) 2021 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 Poole, Logan P. Bock-Hughes, Althea Berardi, Damian E. Macleod, Kay F. ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title | ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title_full | ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title_fullStr | ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title_full_unstemmed | ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title_short | ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3 |
title_sort | ulk1 promotes mitophagy via phosphorylation and stabilization of bnip3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519931/ https://www.ncbi.nlm.nih.gov/pubmed/34654847 http://dx.doi.org/10.1038/s41598-021-00170-4 |
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