Mitochondrial translocator protein (TSPO)

Mitochondrial translocator protein (**TSPO**, formerly known as peripheral benzodiazepine receptor) is an 18 kDa outer mitochondrial membrane transporter highly conserved across species. It is primarily recognized for its role in transporting cholesterol into mitochondria—a critical step for steroid hormone biosynthesis—though recent genetic studies have challenged the absolute necessity of this function. Beyond steroidogenic tissues like adrenal glands and gonads, it is also expressed in the brain where it becomes upregulated during inflammation or injury. In the central nervous system, increased expression marks activated microglia and reactive astrocytes; thus it serves both as a diagnostic biomarker for neuroinflammation and a potential therapeutic target. TSPO participates broadly in regulating mitochondrial homeostasis—including energy metabolism (ATP production), ROS generation/modulation, apoptosis pathways via interaction with components like VDAC/ANT/mPTP complexes—and influences cell proliferation/differentiation. Its ligands are under investigation not only as imaging agents but also therapeutics aiming at conditions such as anxiety disorders, neurodegeneration (Alzheimer’s disease), multiple sclerosis, cardiovascular diseases related to ischemic damage, cancer metabolic shifts (notably glioblastoma), among others. Pharmacologically relevant drugs include classical ligands like PK11195 along with newer compounds such as XBD173 or SSR180575 that modulate its activity. While promising preclinical data exist regarding anti-inflammatory/neuroprotective actions through these agents—by shifting glial activation states or inhibiting apoptotic cascades—the full physiological spectrum remains incompletely defined due to conflicting knockout model results. This complexity underscores both the translational potential and safety challenges associated with targeting this widely distributed multifunctional transporter.

Other names

Translocator proteinPeripheral benzodiazepine receptor (PBR)18 kDa translocator proteinTSPO

- Modulation of cholesterol transport to mitochondria for steroid synthesis via ligand binding to TSPO, affecting steroidogenesis and mitochondrial function. - Reduction of neuroinflammatory cytokines by switching microglia from active to resting state through TSPO ligands. - Inhibition of mitochondrial apoptosis pathway by reducing cytochrome c release with TSPO ligands.