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
  • 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: [email protected].
  • 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: [email protected].
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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