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Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

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Mitochondria adapt to cellular needs by changes in morphology through fusion and fission events, referred to as mitochondrial dynamics. Mitochondrial function and morphology are intimately connected and the dysregulation of mitochondrial dynamics is linked to several human diseases. In this work, we investigated the role of mitochondrial dynamics in wound healing in the Drosophila embryonic epidermis. Mutants for mitochondrial fusion and fission proteins fail to close their wounds, indicating that the regulation of mitochondrial dynamics is required for wound healing. By live-imaging, we found that loss of function of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) compromises the increase of cytosolic and mitochondrial calcium upon wounding and leads to reduced ROS production and F-actin defects at the wound edge, culminating in wound healing impairment. Our results highlight a new role for mitochondrial dynamics in the regulation of calcium, ROS and F-actin during epithelial repair.

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This work was supported by national funds through FCT - Fundação para a Ciência e a Tecnologia, I.P., in the context of a program contract to L. Carvalho (4, 5 and 6 of article 23.º of D.L. no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July), PD/BD/106058/2015 to S. Ponte and PTDC/BIA-BID/29709/2017; the European Research Council (2007-StG-208631) and CONGENTO LISBOA-01-0145-FEDER-022170.

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Calcium Drp1 F-actin Mitochondria Mitochondrial dynamics Wound healing SDG 3 - Good Health and Well-being

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