The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.


Journal

PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755

Informations de publication

Date de publication:
08 2023
Historique:
received: 25 02 2022
accepted: 12 07 2023
revised: 29 08 2023
medline: 31 8 2023
pubmed: 17 8 2023
entrez: 17 8 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37590302
doi: 10.1371/journal.pbio.3002247
pii: PBIOLOGY-D-22-00448
pmc: PMC10465003
doi:

Substances chimiques

ATPases Associated with Diverse Cellular Activities EC 3.6.4.-
Adenosine Triphosphatases EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e3002247

Informations de copyright

Copyright: © 2023 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Jiajia He (J)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Ke Liu (K)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Yifan Wu (Y)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Chenhui Zhao (C)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Shuaijie Yan (S)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Jia-Hui Chen (JH)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China.

Lizhu Hu (L)

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Dongmei Wang (D)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Fan Zheng (F)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Wenfan Wei (W)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Chao Xu (C)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Chengdong Huang (C)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Xing Liu (X)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Xuebiao Yao (X)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Lijun Ding (L)

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Zhiyou Fang (Z)

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Ai-Hui Tang (AH)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China.

Chuanhai Fu (C)

MOE Key Laboratory for Cellular Dynamics & Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Anhui Key Laboratory of Cellular Dynamics and Chemical Biology & Hefei National Research Center for Interdisciplinary Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.

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