Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function

Rumeng Yao; Ruiyuan Pan; Chao Shang; Xiaoheng Li; Jinbo Cheng; Jiangping Xu; Yunfeng Li

doi:10.3389/fphar.2020.00986

Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function

Front Pharmacol. 2020 Jun 30:11:986. doi: 10.3389/fphar.2020.00986. eCollection 2020.

Authors

Rumeng Yao^{1

2}, Ruiyuan Pan³, Chao Shang⁴, Xiaoheng Li⁵, Jinbo Cheng^{6

7}, Jiangping Xu^{1

8}, Yunfeng Li²

Affiliations

¹ Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
² State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
³ The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁴ Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, China.
⁵ The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China.
⁶ Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
⁷ Center on Translational Neuroscience, College of Life & Environmental Science, Minzu University of China, Beijing, China.
⁸ Central Laboratory, Southern Medical University, Guangzhou, China.

Abstract

TSPO is mainly expressed in the mitochondrial outer membrane of microglia in the central nervous system, and its expression is greatly increased when microglia are activated. However, the role and mechanism of this protein in microglial activation is not well characterized. In this study, we investigated the role of TSPO in microglial activation by isolating primary microglia from TSPO knockout mice and constructing TSPO-knockdown microglial cell line. We found that TSPO deficiency significantly inhibited microglial activation induced by LPS or IL-4. Mechanistically, TSPO deficiency greatly decreased the mitochondrial membrane potential and ATP production. Moreover, an analysis of cellular energy metabolism showed that TSPO deficiency suppressed mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in microglial overall metabolic deficits. Together, our results reveal a crucial role of TSPO in microglial activation through the regulation of mitochondrial metabolism, thus providing a potential therapeutic target for neuroinflammation-related diseases of the central nervous system.

Keywords: TSPO; metabolism; microglia; mitochondrial; neuroinflammation; phagocytosis.