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Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy
Mitophagy plays an important role in mitochondrial homeostasis. In yeast, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy. This phosphorylation is counteracted by the yeast equivalent of the STRIPAK complex consisting of the PP2A-like protein phospha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738187/ https://www.ncbi.nlm.nih.gov/pubmed/33317697 http://dx.doi.org/10.7554/eLife.63694 |
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author | Innokentev, Aleksei Furukawa, Kentaro Fukuda, Tomoyuki Saigusa, Tetsu Inoue, Keiichi Yamashita, Shun-ichi Kanki, Tomotake |
author_facet | Innokentev, Aleksei Furukawa, Kentaro Fukuda, Tomoyuki Saigusa, Tetsu Inoue, Keiichi Yamashita, Shun-ichi Kanki, Tomotake |
author_sort | Innokentev, Aleksei |
collection | PubMed |
description | Mitophagy plays an important role in mitochondrial homeostasis. In yeast, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy. This phosphorylation is counteracted by the yeast equivalent of the STRIPAK complex consisting of the PP2A-like protein phosphatase Ppg1 and Far3-7-8-9-10-11 (Far complex), but the underlying mechanism remains elusive. Here we show that two subpopulations of the Far complex reside in the mitochondria and endoplasmic reticulum, respectively, and play distinct roles; the former inhibits mitophagy via Atg32 dephosphorylation, and the latter regulates TORC2 signaling. Ppg1 and Far11 form a subcomplex, and Ppg1 activity is required for the assembling integrity of Ppg1-Far11-Far8. The Far complex preferentially interacts with phosphorylated Atg32, and this interaction is weakened by mitophagy induction. Furthermore, the artificial tethering of Far8 to Atg32 prevents mitophagy. Taken together, the Ppg1-mediated Far complex formation and its dissociation from Atg32 are crucial for mitophagy regulation. |
format | Online Article Text |
id | pubmed-7738187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77381872020-12-16 Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy Innokentev, Aleksei Furukawa, Kentaro Fukuda, Tomoyuki Saigusa, Tetsu Inoue, Keiichi Yamashita, Shun-ichi Kanki, Tomotake eLife Cell Biology Mitophagy plays an important role in mitochondrial homeostasis. In yeast, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy. This phosphorylation is counteracted by the yeast equivalent of the STRIPAK complex consisting of the PP2A-like protein phosphatase Ppg1 and Far3-7-8-9-10-11 (Far complex), but the underlying mechanism remains elusive. Here we show that two subpopulations of the Far complex reside in the mitochondria and endoplasmic reticulum, respectively, and play distinct roles; the former inhibits mitophagy via Atg32 dephosphorylation, and the latter regulates TORC2 signaling. Ppg1 and Far11 form a subcomplex, and Ppg1 activity is required for the assembling integrity of Ppg1-Far11-Far8. The Far complex preferentially interacts with phosphorylated Atg32, and this interaction is weakened by mitophagy induction. Furthermore, the artificial tethering of Far8 to Atg32 prevents mitophagy. Taken together, the Ppg1-mediated Far complex formation and its dissociation from Atg32 are crucial for mitophagy regulation. eLife Sciences Publications, Ltd 2020-12-15 /pmc/articles/PMC7738187/ /pubmed/33317697 http://dx.doi.org/10.7554/eLife.63694 Text en © 2020, Innokentev et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Innokentev, Aleksei Furukawa, Kentaro Fukuda, Tomoyuki Saigusa, Tetsu Inoue, Keiichi Yamashita, Shun-ichi Kanki, Tomotake Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title | Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title_full | Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title_fullStr | Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title_full_unstemmed | Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title_short | Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy |
title_sort | association and dissociation between the mitochondrial far complex and atg32 regulate mitophagy |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738187/ https://www.ncbi.nlm.nih.gov/pubmed/33317697 http://dx.doi.org/10.7554/eLife.63694 |
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