The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

• Published in: The FASEB journal Vol. 34; no. 2; pp. 2055 - 2074
• Main Authors: Huang, Yi‐Fan, Gu, Chang‐Jiang, Wang, Qian, Xu, Lin, Chen, Jian, Zhou, Wei, Zhou, Zheng, Zhao, Shu‐Jie, Li, Lin‐Wei, Kong, Fan‐Qi, Qian, Ding‐Fei, Zhao, Xuan, Fan, Jin, Li, Qing‐Qing, Yin, Guo‐Yong
• Format: Journal Article
• Language: English
• Published: United States 01.02.2020
• Subjects: GIT1; mitophagy; neuron; spinal cord injury; spinal cord injury; neuron; mitophagy; GIT1
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201902047R

In spinal cord ischemia‐reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2–interacting protein‐1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia‐reperfusion. However, the overexpression of adeno‐associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin‐1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN‐induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia‐reperfusion injury and, hence, might serve as a new research site for the protection of ischemia‐reperfusion injury.