Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Phospho-Drp1-637/Fis1/Mid49 Cluster Modulates Mitochondrial Periphery Fission Signature Responses to Mitotic Arrest

Ko Huey Jiun
ORCID logo ,
Cheng Yu Tsai
ORCID logo ,
Thi-Huong Nguyen
ORCID logo ,
Tai-Shan Cheng
,
Chi-Ying F. Huang
ORCID logo ,
Nian-Siou Wu
ORCID logo ,
Chun-Li Su
ORCID logo ,
Po-Yu Tsai
ORCID logo ,
Shean-Jaw Chiou
ORCID logo ,
Ann-Shung Lieu
,
Joon-Khim Loh
* ,
Yi-Ren Hong
*
Version 1 : Received: 10 July 2024 / Approved: 10 July 2024 / Online: 11 July 2024 (12:22:03 CEST)

How to cite: Huey Jiun, K.; Tsai, C. Y.; Nguyen, T.-H.; Cheng, T.-S.; Huang, C.-Y. F.; Wu, N.-S.; Su, C.-L.; Tsai, P.-Y.; Chiou, S.-J.; Lieu, A.-S.; Loh, J.-K.; Hong, Y.-R. The Phospho-Drp1-637/Fis1/Mid49 Cluster Modulates Mitochondrial Periphery Fission Signature Responses to Mitotic Arrest. Preprints 2024, 2024070904. https://doi.org/10.20944/preprints202407.0904.v1 Huey Jiun, K.; Tsai, C. Y.; Nguyen, T.-H.; Cheng, T.-S.; Huang, C.-Y. F.; Wu, N.-S.; Su, C.-L.; Tsai, P.-Y.; Chiou, S.-J.; Lieu, A.-S.; Loh, J.-K.; Hong, Y.-R. The Phospho-Drp1-637/Fis1/Mid49 Cluster Modulates Mitochondrial Periphery Fission Signature Responses to Mitotic Arrest. Preprints 2024, 2024070904. https://doi.org/10.20944/preprints202407.0904.v1

Abstract

Drp1 is considered the master regulator of mitochondrial fission and affects the proper segregation during mitosis. Here, we identified two clusters on mitochondria, including Drp1-Ser-616/Mff/Mid51 and-Drp1-Ser637/Fis1/Mid49 for midzone fission (division) and peripheral fission signatures, respectively. This study revealed that phospho-Drp1-Ser637 is involved in mitigating mitochondrial oxidative stress, resolving a long-standing localization issue. Additionally, we demonstrated that Mid49 and Mid51 exhibit distinct functions in recruiting Drp1 for mitochondrial fission. It also confirmed the essential role of the Fis1 and Mid49 adaptors contributed into mitochondrial fission within the phospho-Drp1-Ser637/Fis1/Mid49 cluster during M-phase. Moreover, it suggested that there is mutual exclusivity between two clusters of phospho-Drp1 with four adaptors on mitochondria, as well as varied responses to specific anti-cancer drugs during mitotic arrest. Remarkably, the upregulation of the spindle assembly checkpoint (SAC) was also observed, ensuring the prolongation of M-phase with the formation of multipolar spindles. Collectively, the phospho-Drp1-637/Fis1/Mid49 cluster may not only function in peripheral fission (mitophagy) but also serve as a key SAC coordinator for the regulation of spindle assembly during mitotic arrest. These findings appear to be mutually exclusive of phospho-Drp1 with four adaptors on mitochondria and vary in response to specific anti-cancer drugs.

Keywords

phospho-Drp1; periphery fission; spindle assembly checkpoint; multipolar spindles; mitotic arrest; anti-cancer drugs

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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