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Mitochondria are a critical metabolic control mechanism for orchestrating phase-specific repair behaviors in wound macrophages

ABSTRACT: Here we demonstrate that skin injury induces different metabolic programs in wound macrophages by profiling their early versus late stages at both the transcriptional and functional levels. We show that glycolytic metabolism in early phase wound macrophages is not sufficient to ensure a productive repair response. Instead, combining conditional disruption of the electron transport chain in myeloid cells by deletion of mitochondrial aspartyl-tRNA synthetase (DARS2) with single cell sequencing analysis of wound macrophages, we found that at early stage a defined subpopulation of macrophages requires repurposing of mitochondrial activity to initiate a cascade of mitochondrial ROS production, HIF1a stabilization, ultimately driving an effective pro-angiogenic transcriptional program essential for timely healing. In contrast, to convey late phase wound macrophages into repair mode they depend on IL-4Ra-mediated mitochondrial respiration and so far unknown regulation of mitohormesis. Collectively, we identify mitochondria as critical metabolic control mechanism for wound macrophage effector functions.

ORGANISM(S): Mus musculus

PROVIDER: GSE183488 | GEO | 2021/10/28

REPOSITORIES: GEO

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Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses in bacterial pneumonia

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2023-12-21 | PXD026934 | Pride

Single cell RNA-seq analyses of dermis from wound day 18 large skin wounds that healed in a fibrotic or regenerative fashion.

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