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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.*

Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing.

Cell Metab. 33, 2398-2414.e9 (2021)

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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 tgcqmitochondrial 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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Metabolism ; Mitochondria ; Mitochondrial Repurposing ; Mitohormesis ; Monocyte/macrophage ; Tissue Repair ; Type 2 Immunity ; Wound Healing; Gene-expression; Rna-seq; Activation; Cell; Angiogenesis; Protein; Oxidation; Mechanism; Succinate; Responses

ISSN (print) / ISBN 1550-4131

e-ISSN 1932-7420

Journal Cell Metabolism

Quellenangaben Volume: 33, Issue: 12, Pages: 2398-2414.e9

Publisher Elsevier

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants DEBRA International Foundation
Center for Molecular Med-icine
Research Unit FOR2240
Germany's Excel-lence Strategy - CECAD, EXC 2030
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC1403
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : Research Unit FOR2599
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC1218
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC829