Maes Margaret E, Colombo Gloria, Schoot Uiterkamp Florianne E, Sternberg Felix, Venturino Alessandro, Pohl Elena E, Siegert Sandra
Institute of Science and Technology Austria (ISTA), Am Campus 1, 3400 Klosterneuburg, Austria.
Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
iScience. 2023 Aug 29;26(10):107780. doi: 10.1016/j.isci.2023.107780. eCollection 2023 Oct 20.
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 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 vs. . 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 , emphasizing the importance of mitochondrial-based sex effects of microglia in other pathologies.
线粒体网络重塑其连接性、内容物和亚细胞定位，以在环境或细胞应激增加的情况下支持优化的能量产生。小胶质细胞依靠线粒体来应对这些应激源，然而我们对线粒体网络及其在小胶质细胞中的适应性了解有限。在这里，我们生成了一个选择性标记小胶质细胞中线粒体的小鼠模型。我们发现，与……相比，线粒体网络更加碎片化，内容物增加且位于核周。视神经挤压后，最接近损伤部位的小胶质细胞中的线粒体网络有类似的适应性变化。通过选择性敲除来阻止损伤后小胶质细胞中UCP2的增加会诱导细胞应激。这导致雄性小胶质细胞中线粒体过度融合，而雌性小胶质细胞由于循环雌激素而不存在这种表型。我们的研究结果为小胶质细胞的线粒体网络分析奠定了基础，强调了小胶质细胞基于线粒体的性别效应在其他病理中的重要性。
