Cell Stress and Chaperones

, Volume 24, Issue 1, pp 235–245 | Cite as

Effects of melatonin on acute brain reperfusion stress: role of Hippo signaling pathway and MFN2-related mitochondrial protection

  • Song LanEmail author
  • Jingfang Liu
  • Xiangying Luo
  • Changlong Bi
Original Paper


Acute brain reperfusion stress is associated with mitochondrial dysfunction through unknown mechanisms. Accordingly, there is no effective drug to control the development and progression of brain reperfusion stress currently. The aim of our investigation is to verify whether melatonin attenuates acute brain reperfusion stress via affecting mitochondrial function. Our studies demonstrated that melatonin treatment suppressed reperfusion-induced neuron death. At the molecular levels, melatonin treatment modulated mitochondrial homeostasis via activating mitochondrial fusion. At the stage of reperfusion, MFN2 expression was downregulated, contributing to mitochondrial fusion inhibition. Interestingly, MFN2-related mitochondrial fusion was reversed by melatonin. Loss of MFN2-related mitochondrial fusion abrogated the protective actions of melatonin on mitochondrial function. Mechanistically, melatonin sustained MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway. Overexpression of Mst1 attenuated the beneficial effects of melatonin on mitochondrial fusion, evoking mitochondrial damage and neuron death in the setting of brain reperfusion stress. Taken together, our results confirmed the protective effects of melatonin on acute brain reperfusion stress. Melatonin treatment activated MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway, finally sustaining mitochondrial function and reducing reperfusion-mediated cerebral injury.


Melatonin Mfn2 Mitochondrial fusion Mst1-Hippo pathway Reperfusion stress 


Author contributions

SL, XYL, CLB, and JFL were involved in the conception and design, performance of experiments, data analysis and interpretation, and manuscript writing. CLB was involved in data analysis and interpretation.

Compliance with ethical standards

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  • Song Lan
    • 1
    Email author
  • Jingfang Liu
    • 1
  • Xiangying Luo
    • 1
  • Changlong Bi
    • 1
  1. 1.Department of Neurosurgery, Xiangya HospitalCentral South UniversityChangshaChina

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