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Publication : Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout.

First Author  Maes ME Year  2023
Journal  iScience Volume  26
Issue  10 Pages  107780
PubMed ID  37731609 Mgi Jnum  J:340755
Mgi Id  MGI:7530444 Doi  10.1016/j.isci.2023.107780
Citation  Maes ME, et al. (2023) Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. iScience 26(10):107780
abstractText  Mitochondrial networks remodel their connectivity, content, and subcellular localization to support optimized energy production in conditions of increased environmental or cellular stress. Microglia rely on mitochondria to respond to these stressors, however our knowledge about mitochondrial networks and their adaptations in microglia in vivo is limited. Here, we generate a mouse model that selectively labels mitochondria in microglia. We identify that mitochondrial networks are more fragmented with increased content and perinuclear localization in vitro vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the injury site after optic nerve crush. Preventing microglial UCP2 increase after injury by selective knockout induces cellular stress. This results in mitochondrial hyperfusion in male microglia, a phenotype absent in females due to circulating estrogens. Our results establish the foundation for mitochondrial network analysis of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects of microglia in other pathologies.
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