Willenborg, Sebastian, Sanin, David E., Jais, Alexander ORCID: 0000-0002-9897-4983, Ding, Xiaolei, Ulas, Thomas, Nuechel, Julian, Popovic, Milica, MacVicar, Thomas, Langer, Thomas, Schultze, Joachim L., Gerbaulet, Alexander, Roers, Axel, Pearce, Edward J., Bruening, Jens C., Trifunovic, Aleksandra and Eming, Sabine A. (2021). Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metab., 33 (12). S. 2398 - 2425. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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 HIF1a stabilization, which ultimately drives a pro-angiogenic program essential for timely healing. In contrast, late-phase, pro-resolving wound macrophages are marked by IL-4Ra-mediated mitochondrial respiration and mitohormesis. Collectively, we identify changes in mitochondrial metabolism as a critical control mechanism for macrophage effector functions during wound healing.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Willenborg, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanin, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jais, AlexanderUNSPECIFIEDorcid.org/0000-0002-9897-4983UNSPECIFIED
Ding, XiaoleiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulas, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuechel, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popovic, MilicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
MacVicar, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze, Joachim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerbaulet, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roers, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, Edward J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eming, Sabine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-599574
DOI: 10.1016/j.cmet.2021.10.004
Journal or Publication Title: Cell Metab.
Volume: 33
Number: 12
Page Range: S. 2398 - 2425
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENE-EXPRESSION; RNA-SEQ; ACTIVATION; CELL; ANGIOGENESIS; PROTEIN; OXIDATION; MECHANISM; SUCCINATE; RESPONSESMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59957

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