RhoA/ROCK Signaling Regulates Drp1-Mediated Mitochondrial Fission During Collective Cell Migration

Frontiers in Cell and Developmental Biology

Yating Kan¹  Hui Zuo¹  Mengqi Wu¹  Jiong Chen¹  Qing Zhang¹  Chen Qu¹  Heng Wang¹  Dou Wang³  Wen Yang⁴ 

[1] Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China;MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China;State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China;

关键词: collective migration;    DRP1;    RhoA/ROCK signaling;    Drosophila border cells;    mitochondrial dynamics;    actomyosin dynamics;   

DOI  :  10.3389/fcell.2022.882581

来源: DOAJ

【 摘 要 】

Collective migration plays critical roles in developmental, physiological and pathological processes, and requires a dynamic actomyosin network for cell shape change, cell adhesion and cell-cell communication. The dynamic network of mitochondria in individual cells is regulated by mitochondrial fission and fusion, and is required for cellular processes including cell metabolism, apoptosis and cell division. But whether mitochondrial dynamics interplays with and regulates actomyosin dynamics during collective migration is not clear. Here, we demonstrate that proper regulation of mitochondrial dynamics is critical for collective migration of Drosophila border cells during oogenesis, and misregulation of fission or fusion results in reduction of ATP levels. Specifically, Drp1 is genetically required for border cell migration, and Drp1-mediated mitochondrial fission promotes formation of leading protrusion, likely through its regulation of ATP levels. Reduction of ATP levels by drug treatment also affects protrusion formation as well as actomyosin dynamics. Importantly, we find that RhoA/ROCK signaling, which is essential for actin and myosin dynamics during border cell migration, could exert its effect on mitochondrial fission through regulating Drp1’s recruitment to mitochondria. These findings suggest that RhoA/ROCK signaling may couple or coordinate actomyosin dynamics with mitochondrial dynamics to achieve optimal actomyosin function, leading to protrusive and migratory behavior.

【 授权许可】

Unknown