Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing
Open accessAbstract
Wound healing is a coordinated process that initially relies on pro-inflammatory macrophages, followed by a pro-resolution function of these cells. Changes in cellular metabolism likely dictate these distinct activities, but the nature of these changes has been unclear. Here, we profiled early- versus late-stage skin wound macrophages in mice at both the transcriptional and functional levels. We found that glycolytic metabolism in the early phase is not sufficient to ensure productive repair. Instead, by combining conditional disruption of the electron transport chain with deletion of mitochondrial aspartyl-tRNA synthetase, followed by single-cell sequencing analysis, we found that a subpopulation of early-stage wound macrophages are marked by mitochondrial ROS (mtROS) production and HIF1α stabilization, which ultimately drives a pro-angiogenic program essential for timely healing. In contrast, late-phase, pro-resolving wound macrophages are marked by IL-4Rα-mediated mitochondrial respiration and mitohormesis. Collectively, we identify changes in mitochondrial metabolism as a critical control mechanism for macrophage effector functions during wound healing.
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Some evidence suggests that a controlled inflammatory response may be necessary to initiate repair in acute liver injury.
“However, whether all these pro-inflammatory subsets are entirely detrimental remains unclear, as some evidence suggests that a controlled inflammatory response may be necessary to initiate repair (42, 43).”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [42]
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- Authors
- Willenborg, S., Sanin, D. E., Jais, A., Ding, X., Ulas, T., Nüchel, J., Popović, M., MacVicar, T., Langer, T., Schultze, J. L., Gerbaulet, A., Roers, A., Pearce, E. J., Brüning, J. C., Trifunovic, A., & Eming, S. A.
- Affiliations
- University of Cologne (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- University of Bonn (DE)
- Max Planck Institute for Biology of Ageing (DE)
- Technische Universität Dresden (DE)
- University of Freiburg (DE)
- Corresponding author
- Eming, Sabine A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 33
- Issue
- 12
- Pages
- 2398-2414.e9
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3209103161
- Cited by
- 310
- References
- 19
- Citations by year
- 2026: 81 · 2025: 82 · 2024: 71 · 2023: 47 · 2022: 28 · 2021: 1
- FWCI
- 19.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- DZNE Pub (submittedVersion, cc-by)
- Funders
- Eterna International Foundation
- Deutsche Forschungsgemeinschaft (EXC 2030 – 390661388)
- University of Cologne Center for Molecular Medicine Cologne
- DEBRA International
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- wound healing, macrophages, mitochondrial metabolism, mitochondrial reactive oxygen species, HIF-1α stabilization, electron transport chain, aspartyl-tRNA synthetase, glycolysis, angiogenesis, IL-4 receptor alpha, mitohormesis, skin wound healing, single-cell transcriptomics
- MeSH terms
- Animals, Macrophages, Mitochondria, Wound Healing, Mice
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