TY  - JOUR
AU  - Willenborg, Sebastian
AU  - Sanin, David E
AU  - Jais, Alexander
AU  - Ding, Xiaolei
AU  - Ulas, Thomas
AU  - Nüchel, Julian
AU  - Popović, Milica
AU  - MacVicar, Thomas
AU  - Langer, Thomas
AU  - Schultze, Joachim L
AU  - Gerbaulet, Alexander
AU  - Roers, Axel
AU  - Pearce, Edward J
AU  - Brüning, Jens C
AU  - Trifunovic, Aleksandra
AU  - Eming, Sabine A
TI  - Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing.
JO  - Cell metabolism
VL  - 33
IS  - 12
SN  - 1550-4131
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DZNE-2022-00158
SP  - 2398 - 2414.e9
PY  - 2021
N1  - (CC BY)
AB  - 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.
KW  - Animals
KW  - Macrophages: metabolism
KW  - Mice
KW  - Mitochondria: metabolism
KW  - Wound Healing
KW  - metabolism (Other)
KW  - mitochondria (Other)
KW  - mitochondrial repurposing (Other)
KW  - mitohormesis (Other)
KW  - monocyte/macrophage (Other)
KW  - tissue repair (Other)
KW  - type 2 immunity (Other)
KW  - wound healing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34715039
DO  - DOI:10.1016/j.cmet.2021.10.004
UR  - https://pub.dzne.de/record/163396
ER  -