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The dominant-negative mitochondrial calcium uniporter subunit MCUb drives macrophage polarization during skeletal muscle regeneration
- Publication Year :
- 2021
-
Abstract
- Damaged skeletal muscle can regenerate because of the coordinated action of immune cells with muscle stem cells, called satellite cells. Proinflammatory macrophages infiltrate skeletal muscle soon after injury to sustain the proliferation of satellite cells. These macrophages later acquire the anti-inflammatory phenotype and promote the differentiation and fusion of satellite cells. Here, we showed that MCUb, the dominant-negative subunit of the mitochondrial calcium uniporter (MCU) complex, promotes muscle regeneration by controlling macrophage responses. Macrophages lacking MCUb lost the ability to efficiently acquire the anti-inflammatory profile, and mice with MCUb-deficient macrophages showed delayed regeneration through exhaustion of the satellite cell pool. MCUb ablation altered macrophage metabolism by promoting glycolysis and the accumulation of TCA cycle intermediates, which was accompanied by the stabilization of HIF-1α, the master transcriptional regulator of the macrophage proinflammatory program. Together, these data demonstrate that MCUb abundance is tightly controlled in macrophages to enable satellite cell functional differentiation and recovery of tissue homeostasis after damage.
- Subjects :
- Chemistry
Protein subunit
Regeneration (biology)
Macrophages
Dominant negative
Macrophage polarization
food and beverages
Skeletal muscle
Cell Biology
Biochemistry
Proinflammatory cytokine
Cell biology
medicine.anatomical_structure
Immune system
medicine
Calcium
Calcium Channels
Stem cell
Muscle, Skeletal
Molecular Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3ca964f794f9ff6efe1918f7bcf6c6f4