2. Academic Validation
  3. Upregulation of mitochondrial PGK1 by ROS-TBC1D15 pathway promotes neuronal death after oxygen-glucose deprivation/reoxygenation injury

Upregulation of mitochondrial PGK1 by ROS-TBC1D15 pathway promotes neuronal death after oxygen-glucose deprivation/reoxygenation injury

  • Brain Res. 2023 Dec 16:1825:148724. doi: 10.1016/j.brainres.2023.148724.
Songfeng Chen 1,  Hui Wang 2,  Juan Chen 3,  Jing Cheng 1,  Jingchen Gao 2,  Shujun Chen 2,  Xujin Yao 2,  Jiangdong Sun 2,  Jinyang Ren 2,  Shifang Li 2,  Fengyuan Che 4,  Qi Wan 5
Affiliations

Affiliations

  • 1 Department of Physiology, School of Medicine, Wuhan University, Wuhan, China.
  • 2 Institute of Neuroregeneration & Neurorehabilitation, School of Basic Medicine, Qingdao University, Qingdao, China.
  • 3 Department of Neurology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
  • 4 Central Laboratory, Department of Neurology, Linyi People's Hospital, Qingdao University, Linyi, China. Electronic address: che1971@126.com.
  • 5 Department of Physiology, School of Medicine, Wuhan University, Wuhan, China; Institute of Neuroregeneration & Neurorehabilitation, School of Basic Medicine, Qingdao University, Qingdao, China. Electronic address: qiwan1@hotmail.com.
PMID: 38110073 DOI: 10.1016/j.brainres.2023.148724
Abstract

Phosphoglycerate kinase 1 (PGK1) is extensively located in the cytosol and mitochondria. The role of PGK1 in ischemic neuronal injury remains elusive. In the in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R), we showed that PGK1 expression was increased in cortical neurons. Knockdown of PGK1 led to a reduction of OGD/R-induced neuronal death. The expression of cytosolic PGK1 was reduced, but the levels of mitochondrial PGK1 were increased in OGD/R-insulted neurons. Inhibiting the activity of mitochondrial PGK1 alleviated the neuronal injury after OGD/R insult. We further showed that the protein levels of TBC domain family member 15 (TBC1D15) were decreased in OGD/R-insulted neurons. Knockdown of TBC1D15 led to increased levels of mitochondrial PGK1 after OGD/R insult in cortical neurons. Moreover, increased Reactive Oxygen Species (ROS) resulted in a reduction of TBC1D15 in OGD/R-insulted neurons. These results suggest that the upregulation of mitochondrial PGK1 by ROS-TBC1D15 signaling pathway promotes neuronal death after OGD/R injury. Mitochondrial PGK1 may act as a regulator of neuronal survival and interventions in the PGK1-dependent pathway may be a potential therapeutic strategy.

Keywords

Mitochondria; Oxygen-glucose deprivation/reoxygenation; Phosphoglycerate Kinase 1; Reactive oxygen species; TBC domain family member 15.

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