Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, VA, 22908-0710, USA.
Genetically Engineered Murine Model Core, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Cell Mol Life Sci. 2019 Apr;76(7):1381-1396. doi: 10.1007/s00018-019-03007-6. Epub 2019 Jan 21.
Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a component of the complex III in the respiratory chain. Its biological functions are unknown. Here, we showed that knockout of UQCRC1 led to embryonic lethality. Disrupting one UQCRC1 allele in mice (heterozygous mice) of both sexes did not affect their growth but reduced UQCRC1 mRNA and protein in the brain. These mice had decreased complex III formation, complex III activity and ATP content in the brain at baseline. They developed worsened neurological outcome after brain ischemia/hypoxia or focal brain ischemia compared with wild-type mice. The ischemic cerebral cortex of the heterozygous mice had decreased mitochondrial membrane potential and ATP content as well as increased free radicals. Also, the heterozygous mice performed poorly in the Barnes maze and novel object recognition tests. Finally, UQCRC1 was expressed abundantly in neurons and astrocytes. These results suggest a critical role of UQCRC1 in embryo survival. UQCRC1 may also be important by forming the complex III to maintain normal brain ischemic tolerance, learning and memory.
泛醌细胞色素 c 还原酶核心蛋白 I（UQCRC1）是呼吸链复合物 III 的一个组成部分。其生物学功能尚不清楚。在这里，我们发现 UQCRC1 敲除导致胚胎致死。破坏雌雄两性小鼠的一个 UQCRC1 等位基因（杂合子小鼠）并不影响其生长，但会降低大脑中的 UQCRC1 mRNA 和蛋白。这些小鼠在基线时大脑中的复合物 III 形成、复合物 III 活性和 ATP 含量降低。与野生型小鼠相比，它们在脑缺血/缺氧或局灶性脑缺血后出现更严重的神经功能障碍。杂合子小鼠的缺血性大脑皮层的线粒体膜电位和 ATP 含量降低，自由基增加。此外，杂合子小鼠在 Barnes 迷宫和新物体识别测试中表现不佳。最后，UQCRC1 在神经元和星形胶质细胞中大量表达。这些结果表明 UQCRC1 在胚胎存活中起关键作用。UQCRC1 可能通过形成复合物 III 来维持正常的脑缺血耐受、学习和记忆，因此也很重要。
