Journal article
mTor limits autophagy to facilitate cell volume expansion and rapid wound repair in Drosophila embryos
Developmental cell, Vol.60(10), pp.1400-1410.e3
05/2025
DOI: 10.1016/j.devcel.2024.12.039
PMID: 39824179
Abstract
Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the increase in the volume of the cells adjacent to the wound. The mechanistic target of rapamycin (mTor) complex 1 (TORC1) is associated with cell growth. We found that disrupting TORC1 signaling in Drosophila embryos prevented cell volume increases and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Five-dimensional microscopy demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. mTor inhibition increased autophagy, and activating autophagy prevented cell volume expansion and slowed down wound closure. Finally, reducing autophagy in embryos with disrupted TORC1 signaling rescued cell volume changes and rapid wound repair. Together, our results show that TORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the increase in the volume of the cells adjacent to the wound. The mechanistic target of rapamycin (mTor) complex 1 (TORC1) is associated with cell growth. We found that disrupting TORC1 signaling in Drosophila embryos prevented cell volume increases and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Five-dimensional microscopy demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. mTor inhibition increased autophagy, and activating autophagy prevented cell volume expansion and slowed down wound closure. Finally, reducing autophagy in embryos with disrupted TORC1 signaling rescued cell volume changes and rapid wound repair. Together, our results show that TORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.
Details
- Title: Subtitle
- mTor limits autophagy to facilitate cell volume expansion and rapid wound repair in Drosophila embryos
- Creators
- Gordana Scepanovic - University of TorontoNegar Balaghi - University of TorontoKatheryn E Rothenberg - University of TorontoRodrigo Fernandez-Gonzalez - Ted Rogers Centre for Heart Research
- Resource Type
- Journal article
- Publication Details
- Developmental cell, Vol.60(10), pp.1400-1410.e3
- DOI
- 10.1016/j.devcel.2024.12.039
- PMID
- 39824179
- NLM abbreviation
- Dev Cell
- ISSN
- 1878-1551
- eISSN
- 1878-1551
- Publisher
- CELL PRESS
- Grant note
- Ontario Graduate ScholarshipAlexander Graham Bell Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC)Canadian Institutes of Health Research: 186188 Ted Rogers Centre for Heart ResearchNSERC: 418-438-13 Canada Foundation for Innovation: 30279 Translational Biology and Engineering Program from the Ted Rogers Centre for Heart Research
We are grateful to Tony Harris, Ran Kafri, Ashley Bruce, Ana Maria do Carmo, and Veronica Castle for comments on the manuscript; Michael Galko and Jonathan Palozzi for useful discussions; and Thomas Hurd and Gabor Juhasz for reagents and flies. Flybase provided important information for this study. G.S. was supported by an Ontario Graduate Scholarship and an Alexander Graham Bell Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC) . N.B. was supported by an Ontario Graduate Scholarship. K.E.R. was supported by postdoctoral fellowships from the Canadian Institutes of Health Research and the Ted Rogers Centre for Heart Research. Our research is funded by grants to R.F.-G. from the Canadian Institutes of Health Research (156279 and 186188) , NSERC (418-438-13) , the Canada Foundation for Innovation (30279) , and the Translational Biology and Engineering Program from the Ted Rogers Centre for Heart Research. R.F.-G. is the Canada Research Chair in Quantitative Cell Biology and Morphogenesis.
- Language
- English
- Electronic publication date
- 01/10/2025
- Date published
- 05/2025
- Academic Unit
- Biology
- Record Identifier
- 9984773413302771
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