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Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice
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Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice
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Journal Article
Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice
2019
Overview
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.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Adenosine Triphosphate - metabolism
/ alleles
/ Animals
/ Biomedical and Life Sciences
/ Brain
/ death
/ Electron Transport Complex III - antagonists & inhibitors
/ Electron Transport Complex III - genetics
/ Electron Transport Complex III - metabolism
/ Embryo, Mammalian - metabolism
/ Embryos
/ Female
/ Hypoxia
/ Ischemia
/ Learning
/ Male
/ Membrane Potential, Mitochondrial
/ Memory
/ Mice
/ mRNA
/ neurons
/ Proteins
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Survival
