Tspo, also known as the 18 kDa translocator protein and formerly called the peripheral benzodiazepine receptor, is an evolutionarily conserved protein located in the outer mitochondrial membrane [2,3,4]. It is implicated in the regulation of many cellular processes, such as inflammatory responses, oxidative stress, and mitochondrial homeostasis. Tspo ligands are used as diagnostic biomarkers, especially in glioma and neuroinflammation studies. Tspo's functions may be related to stress-induced metabolic changes, and it may act through associations with protein binding partners or ligands [2].

Tspo deficiency, studied in knockout xenograft and spontaneous mouse glioma models, promoted glioma cell proliferation in vitro and glioma growth and angiogenesis in vivo. Loss of Tspo led to mitochondrial fragmentation, increased glucose uptake, lactic acid conversion, decreased oxidative phosphorylation, and increased glycolysis, indicating that Tspo serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis [1].

In conclusion, Tspo is crucial for maintaining mitochondrial function and metabolic balance. The Tspo knockout mouse models have revealed its significant role in glioma, highlighting its potential as a therapeutic target for glioma treatment. These models contribute to understanding the molecular mechanisms underlying glioma development, providing insights into potential treatment strategies targeting Tspo-regulated pathways [1].

References:

1. Fu, Yi, Wang, Dongdong, Wang, Huaishan, He, Wei, Zhang, Jianmin. . TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma. In Neuro-oncology, 22, 240-252. doi:10.1093/neuonc/noz183. https://pubmed.ncbi.nlm.nih.gov/31563962/

2. Hiser, Carrie, Montgomery, Beronda L, Ferguson-Miller, Shelagh. 2021. TSPO protein binding partners in bacteria, animals, and plants. In Journal of bioenergetics and biomembranes, 53, 463-487. doi:10.1007/s10863-021-09905-4. https://pubmed.ncbi.nlm.nih.gov/34191248/

3. Bonsack, Frederick, Sukumari-Ramesh, Sangeetha. 2018. TSPO: An Evolutionarily Conserved Protein with Elusive Functions. In International journal of molecular sciences, 19, . doi:10.3390/ijms19061694. https://pubmed.ncbi.nlm.nih.gov/29875327/

4. Nutma, Erik, Ceyzériat, Kelly, Amor, Sandra, Papadopoulos, Vassilios, Tournier, Benjamin B. 2021. Cellular sources of TSPO expression in healthy and diseased brain. In European journal of nuclear medicine and molecular imaging, 49, 146-163. doi:10.1007/s00259-020-05166-2. https://pubmed.ncbi.nlm.nih.gov/33433698/