Journal Article

DZNE-2022-00158

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing.

Willenborg, S. ; Sanin, D. E. ; Jais, A. ; Ding, X. ; Ulas, T.DZNE* ; Nüchel, J. ; Popović, M. ; MacVicar, T. ; Langer, T. ; Schultze, J. L.DZNE* ; Gerbaulet, A. ; Roers, A. ; Pearce, E. J. ; Brüning, J. C. ; Trifunovic, A. ; Eming, S. A.

2021
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.cmet.2021.10.004

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.

Keyword(s): Animals (MeSH) ; Macrophages: metabolism (MeSH) ; Mice (MeSH) ; Mitochondria: metabolism (MeSH) ; Wound Healing (MeSH) ; metabolism ; mitochondria ; mitochondrial repurposing ; mitohormesis ; monocyte/macrophage ; tissue repair ; type 2 immunity ; wound healing

Note: (CC BY)

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Contributing Institute(s):

1. United epigenomic platform (AG Schultze)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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