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Abstract
ABSTRACTMitochondria 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.
Highlights
Mitochondria perform critical cellular functions such as energy production, regulation of calcium (Ca2+), redox homeostasis and cell death (El-Hattab and Scaglia, 2016)
Mitochondrial dynamics proteins are required for wound healing To test whether the mitochondrial dynamics machinery (Fig. 1A) is required for epithelial repair, we performed a previously described wounding assay in the Drosophila embryonic epidermis (Campos et al, 2010)
We tested other fission regulators: Fission protein 1 (Fis1), which acts as a receptor for Dynamin-related protein 1 (Drp1) at the OMM (Losón et al, 2013), and Ganglioside-induced differentiation associated protein 1 (GDAP1), whose function is not well understood (Huber et al, 2013)
Summary
Mitochondria perform critical cellular functions such as energy production, regulation of calcium (Ca2+), redox homeostasis and cell death (El-Hattab and Scaglia, 2016). Mitochondrial shape is controlled by antagonizing fusion and fission events (Lewis and Lewis, 1914; Nunnari et al, 1997), described as mitochondrial dynamics, which allow mitochondria to adapt to cellular demands (Nunnari and Suomalainen, 2012). Dynamin-related proteins regulate mitochondrial dynamics through their GTPase activity (Hoppins et al, 2007). Mitochondrial fission is accomplished by Dynamin-related protein 1 (Drp). Drp is recruited from the cytosol to the mitochondria, oligomerizes and constricts this organelle until its division is achieved (Bleazard et al, 1999; Labrousse et al, 1999; Smirnova et al, 2001; Yoon et al, 2001).
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