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

Biol Open. 2020 May 3;9(5):bio048629. doi: 10.1242/bio.048629.

Abstract

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 reactive oxygen species (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.

Keywords: Calcium; Drp1; F-actin; Mitochondria; Mitochondrial dynamics; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Biomarkers
  • Calcium / metabolism*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Drosophila
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Immunohistochemistry
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Dynamics / genetics*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation
  • Reactive Oxygen Species / metabolism
  • Wound Healing / genetics*

Substances

  • Actins
  • Biomarkers
  • Cytoskeletal Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • DRP1 protein, Drosophila
  • GTP-Binding Proteins
  • Calcium