Home > Publications Database > Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. > print

001     163396
005     20240320115517.0
024 7 _ |a 10.1016/j.cmet.2021.10.004
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024 7 _ |a pmid:34715039
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024 7 _ |a 1550-4131
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024 7 _ |a 1932-7420
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037 _ _ |a DZNE-2022-00158
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Willenborg, Sebastian
|b 0
245 _ _ |a Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing.
260 _ _ |a Cambridge, Mass.
|c 2021
|b Cell Press
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520 _ _ |a 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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650 _ 7 |a metabolism
|2 Other
650 _ 7 |a mitochondria
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650 _ 7 |a mitochondrial repurposing
|2 Other
650 _ 7 |a mitohormesis
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650 _ 7 |a monocyte/macrophage
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650 _ 7 |a tissue repair
|2 Other
650 _ 7 |a type 2 immunity
|2 Other
650 _ 7 |a wound healing
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
650 _ 2 |a Wound Healing
|2 MeSH
700 1 _ |a Sanin, David E
|b 1
700 1 _ |a Jais, Alexander
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700 1 _ |a Ding, Xiaolei
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700 1 _ |a Ulas, Thomas
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700 1 _ |a Nüchel, Julian
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700 1 _ |a Popović, Milica
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700 1 _ |a MacVicar, Thomas
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700 1 _ |a Langer, Thomas
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Gerbaulet, Alexander
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700 1 _ |a Roers, Axel
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700 1 _ |a Pearce, Edward J
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700 1 _ |a Brüning, Jens C
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700 1 _ |a Trifunovic, Aleksandra
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700 1 _ |a Eming, Sabine A
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773 _ _ |a 10.1016/j.cmet.2021.10.004
|g Vol. 33, no. 12, p. 2398 - 2414.e9
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