The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Cell Cycle Pub Date : 2023-11-01 Epub Date: 2024-01-18 DOI:10.1080/15384101.2023.2289753
Nian-Siou Wu, I-Chu Ma, Yi-Fan Lin, Huey-Jiun Ko, Joon-Khim Loh, Yi-Ren Hong
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Abstract

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.

细胞周期中磷酸化-Drp1与四个适配器的奥秘:线粒体分裂与细胞命运决定的耦合。
最近的研究加深了我们对线粒体动力学的认识,将线粒体裂变分为两种类型。为了进一步阐明两种不同裂变机制与 Drp1 四大适配体之间的关系,我们提出了一个机制模型,阐明了磷酸化-Drp1 与其适配体在细胞周期中的多种功能,并深入揭示了其分子基础和进化意义。该模型不仅强调了不同磷酸化Drp1与线粒体促裂变适配子集各自的聚类特征,而且还强调了在不同的关键裂变过程中,磷酸化Drp1-适配子不同聚类之间的相关性、串联性和转移性。特别是,磷酸化Drp1(Ser616)与Mff/MiD51耦合以执行线粒体分裂,磷酸化Drp1(Ser637)与MiD49/Fis1耦合以在M期执行有丝分裂。然后,我们将该模型用于研究线粒体动力学与帕金森病(PD)和癌变之间的关系。我们提出的模型确实与当前的研究成果和病理观察结果相吻合,为未来的治疗设计提供了很好的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Cycle
Cell Cycle 生物-细胞生物学
CiteScore
7.70
自引率
2.30%
发文量
281
审稿时长
1 months
期刊介绍: Cell Cycle is a bi-weekly peer-reviewed journal of high priority research from all areas of cell biology. Cell Cycle covers all topics from yeast to man, from DNA to function, from development to aging, from stem cells to cell senescence, from metabolism to cell death, from cancer to neurobiology, from molecular biology to therapeutics. Our goal is fast publication of outstanding research.
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