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Cellular and Molecular Life Sciences

, Volume 76, Issue 7, pp 1381–1396 | Cite as

Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice

  • Weiran Shan
  • Jun Li
  • Wenhao Xu
  • Hong Li
  • Zhiyi ZuoEmail author
Original Article
  • 126 Downloads

Abstract

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.

Keywords

Brain ischemia Complex III Learning and memory Ubiquinol cytochrome c reductase core protein I 

Abbreviations

UQCRC1

Ubiquinol cytochrome c reductase core protein I

UQCRC2

Ubiquinol cytochrome c reductase core protein 2

MAP-2

Microtubule associated protein 2

GFAP

Glial fibrillary acidic protein

Iba-1

Ionized calcium-binding adaptor molecule 1

TMEM119

Transmembrane protein 119

MCAO

Middle cerebral arterial occlusion

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

TTC

2,3,5-Triphenyltetrazolium chloride

ROS

Reactive oxygen species

Notes

Acknowledgements

This study was supported by Grants (GM098308, AG056995, HD089999 and NS099118) from the National Institutes of General Medical Sciences and National Institutes of Health, Bethesda, MD, the Robert M. Epstein Professorship endowment, University of Virginia, Charlottesville, VA.

Author contributions

ZZ conceived the project. WS, JL, WX, HL and ZZ designed the study, WS, JL and WX performed the experiments. WS did the initial data analysis and drafted Methods section. ZZ performed the final data analysis and wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Weiran Shan
    • 1
  • Jun Li
    • 1
  • Wenhao Xu
    • 3
  • Hong Li
    • 4
  • Zhiyi Zuo
    • 1
    • 2
    Email author
  1. 1.Department of AnesthesiologyUniversity of Virginia Health SystemCharlottesvilleUSA
  2. 2.Department of Neuroscience and Neurological SurgeryUniversity of VirginiaCharlottesvilleUSA
  3. 3.Genetically Engineered Murine Model Core, School of MedicineUniversity of VirginiaCharlottesvilleUSA
  4. 4.Department of Anesthesiology, Xinqiao HospitalThird Military Medical UniversityChongqingChina

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