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bioRxiv · 10.1101/2023.10.10.561758

mTOR inhibits autophagy to facilitate cell swelling and rapid wound repair

Scepanovic, G.·Fernandez-Gonzalez, R.
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Abstract

Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the swelling of the cells adjacent to the wound. The mechanistic target of rapamycin complex 1 (mTORC1) is often associated with cell growth. We found that disrupting mTORC1 signalling prevented cell swelling and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Using five-dimensional time-lapse microscopy, as well as pharmacological and genetic manipulations, we demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. Quantitative image analysis showed that mTOR inhibition increased autophagy, and that activating autophagy prevented cell swelling and slowed down embryonic wound closure. Finally, reducing autophagy in embryos in which mTORC1 signalling was disrupted rescued rapid wound repair. Together, our results show that mTORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.

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Scepanovic, G., Fernandez-Gonzalez, R.. 2023-10-10. mTOR inhibits autophagy to facilitate cell swelling and rapid wound repair. https://doi.org/10.1101/2023.10.10.561758

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