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Neurotoxicity Research

, Volume 35, Issue 2, pp 331–343 | Cite as

Mutual Antagonism of PINK1/Parkin and PGC-1α Contributes to Maintenance of Mitochondrial Homeostasis in Rotenone-Induced Neurotoxicity

  • Kaige Peng
  • Jingsong Xiao
  • Likui Yang
  • Feng Ye
  • Jia Cao
  • Yan SaiEmail author
ORIGINAL ARTICLE

Abstract

Parkinson’s disease (PD) is a progressive, selective, and age-related neurodegenerative disease. The pathogenic focus of PD is mitochondrial dysfunction. When mitochondrial homeostasis was damaged, it can lead to reactive oxygen species formation to further accelerate the accumulation of dysfunctional mitochondria, resulting in a vicious cycle harmful to the neuron. PINK1 and Parkin, two proteins that are linked to PD, play vital roles in mitophagy, which was very important in maintaining mitochondrial homeostasis. Thus, at present, we explored mitochondrial biogenesis, mitophagy, and fission/fusion in rotenone-induced dopamine neurotoxicity. In particular, we focused on interactions between the PINK1/Parkin pathway and PGC-1α in the regulation of mitochondrial homeostasis impairment. The results indicated that both the autophagy and mitophagy levels increased significantly and were accompanied by altered levels of PINK1/Parkin proteins in rotenone-induced neurotoxicity. PINK1 influenced mitochondrial biogenesis by inhibiting PGC-1α and mtTFA protein expression as well as the mtDNA copy number. PGC-1α, in turn, inhibited PINK1/Parkin protein expression and the mitophagy levels. Furthermore, the results demonstrated that PINK1 influenced mitochondrial fission/fusion by regulating MFN2 and phosphorylating Drp1. In summary, mutual antagonism of the PINK1/Parkin pathway and PGC-1α formed a balance that regulated mitochondrial biogenesis, fission/fusion, and mitophagy. These effects contributed to the maintenance of mitochondrial homeostasis in rotenone-induced neurotoxicity.

Keywords

Rotenone PINK1/Parkin Mitophagy PGC-1α Mitochondrial biogenesis Mitochondrial fission/fusion 

Notes

Acknowledgements

The authors thank Dr. Jian Wang and Mrs. Qin Zhang for their help with the observation of mitophagy under confocal laser microscopy.

Funding

This work was supported by grants from the NSFC (Natural Science Foundation of China) (81473006, 81273106) to Yan Sai.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kaige Peng
    • 1
  • Jingsong Xiao
    • 1
  • Likui Yang
    • 1
  • Feng Ye
    • 1
  • Jia Cao
    • 1
  • Yan Sai
    • 1
    Email author
  1. 1.Institute of Toxicology, College of Preventive MedicineThird Military Medical UniversityChongqingPeople’s Republic of China

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