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

Autor:	Wu NS; Department of Education, Hsin-Chu Branch, National Taiwan University Hospital, Hsinchu, Taiwan.; PhD Program in Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan., Ma IC; Division of Neurology, China Medical University Hospital, Taichung, Taiwan., Lin YF; Department of Education, National Taiwan University Hospital, Taipei, Taiwan., Ko HJ; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Loh JK; Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Hong YR; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Graduate Institutes of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.; Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jazyk:	angličtina
Zdroj:	Cell cycle (Georgetown, Tex.) [Cell Cycle] 2023 Nov; Vol. 22 (21-22), pp. 2485-2503. Date of Electronic Publication: 2024 Jan 18.
DOI:	10.1080/15384101.2023.2289753
Abstrakt:	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.
Databáze:	MEDLINE
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