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@ARTICLE{Willenborg:163396,
author = {Willenborg, Sebastian and Sanin, David E and Jais,
Alexander and Ding, Xiaolei and Ulas, Thomas and Nüchel,
Julian and Popović, Milica and MacVicar, Thomas and Langer,
Thomas and Schultze, Joachim L and Gerbaulet, Alexander and
Roers, Axel and Pearce, Edward J and Brüning, Jens C and
Trifunovic, Aleksandra and Eming, Sabine A},
title = {{M}itochondrial metabolism coordinates stage-specific
repair processes in macrophages during wound healing.},
journal = {Cell metabolism},
volume = {33},
number = {12},
issn = {1550-4131},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DZNE-2022-00158},
pages = {2398 - 2414.e9},
year = {2021},
note = {(CC BY)},
abstract = {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.},
keywords = {Animals / Macrophages: metabolism / Mice / Mitochondria:
metabolism / Wound Healing / metabolism (Other) /
mitochondria (Other) / mitochondrial repurposing (Other) /
mitohormesis (Other) / monocyte/macrophage (Other) / tissue
repair (Other) / type 2 immunity (Other) / wound healing
(Other)},
cin = {AG Schultze},
ddc = {570},
cid = {I:(DE-2719)1013031},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34715039},
doi = {10.1016/j.cmet.2021.10.004},
url = {https://pub.dzne.de/record/163396},
}