18 kDa translocator protein – implications in cell’s functions
Agnieszka Kołodziejczyk 1Abstract
The mitochondrial 18kDa Translocation Protein (TSPO) was first identified in 1977 by its capability to bind benzodiazepines in peripheral tissues. It is more commonly known after its previous name – peripheral benzodiazepine receptor (PBR) as opposed to the central benzodiazepine receptor (CBR), from which it differs by location, structure and function. It is ubiquitous with highest expression in steroid-producing tissues, like adrenal cortex, ovaries, testicles, and placenta. The role of TSPO is crucial for living; its inactivation results in early embryonic-lethal phenotype in mice. TSPO has been implicated in various functions of cell, including steroidogenesis, cellular respiration, reactive oxygen species production, heme biosynthesis, immunomodulation, apoptosis, and cellular proliferation. TSPO has been shown to interact with other cellular proteins: 32 kDa voltage-dependent anion channel (VDAC), 30 kDa adenine nucleotide translocase (ANT), cyclophilin D, hexokinase, creatinine kinase, diazepam binding inhibitor (DBI), phosphate carrier and Bcl-2 family. They are – involved in the formation and regulation of mitochondrial permeability transition pore (mPTP) at the junction of the inner and outer mitochondrial membranes. While the function and characteristics of the mPTP are known, its well defined, but its structure remains speculative. Changes in TSPO expression are associated with multiple disorders, including cancer, ischaemia-reperfusion injury, neurological diseases and psychiatric disorders, atheromatosis, and others. – TSPO is able to bind cholesterol, porphyrins and other ligands with different affinity. The current knowledge of TSPO implicates its potential use as a diagnostic marker and therapeutic target in different diseases and their therapies.
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