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The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission
Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report tha...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465003/ https://www.ncbi.nlm.nih.gov/pubmed/37590302 http://dx.doi.org/10.1371/journal.pbio.3002247 |
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author | He, Jiajia Liu, Ke Wu, Yifan Zhao, Chenhui Yan, Shuaijie Chen, Jia-Hui Hu, Lizhu Wang, Dongmei Zheng, Fan Wei, Wenfan Xu, Chao Huang, Chengdong Liu, Xing Yao, Xuebiao Ding, Lijun Fang, Zhiyou Tang, Ai-Hui Fu, Chuanhai |
author_facet | He, Jiajia Liu, Ke Wu, Yifan Zhao, Chenhui Yan, Shuaijie Chen, Jia-Hui Hu, Lizhu Wang, Dongmei Zheng, Fan Wei, Wenfan Xu, Chao Huang, Chengdong Liu, Xing Yao, Xuebiao Ding, Lijun Fang, Zhiyou Tang, Ai-Hui Fu, Chuanhai |
author_sort | He, Jiajia |
collection | PubMed |
description | Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission. |
format | Online Article Text |
id | pubmed-10465003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104650032023-08-30 The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission He, Jiajia Liu, Ke Wu, Yifan Zhao, Chenhui Yan, Shuaijie Chen, Jia-Hui Hu, Lizhu Wang, Dongmei Zheng, Fan Wei, Wenfan Xu, Chao Huang, Chengdong Liu, Xing Yao, Xuebiao Ding, Lijun Fang, Zhiyou Tang, Ai-Hui Fu, Chuanhai PLoS Biol Research Article Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission. Public Library of Science 2023-08-17 /pmc/articles/PMC10465003/ /pubmed/37590302 http://dx.doi.org/10.1371/journal.pbio.3002247 Text en © 2023 He et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article He, Jiajia Liu, Ke Wu, Yifan Zhao, Chenhui Yan, Shuaijie Chen, Jia-Hui Hu, Lizhu Wang, Dongmei Zheng, Fan Wei, Wenfan Xu, Chao Huang, Chengdong Liu, Xing Yao, Xuebiao Ding, Lijun Fang, Zhiyou Tang, Ai-Hui Fu, Chuanhai The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title | The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title_full | The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title_fullStr | The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title_full_unstemmed | The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title_short | The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
title_sort | aaa-atpase yta4/atad1 interacts with the mitochondrial divisome to inhibit mitochondrial fission |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465003/ https://www.ncbi.nlm.nih.gov/pubmed/37590302 http://dx.doi.org/10.1371/journal.pbio.3002247 |
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