Translocator protein

TSTT (abbreviation of Engl. Translocator protein or tryptophan -rich sensory protein), also known as peripheral benzodiazepine receptor ( PBR), is a transmembrane protein of the outer mitochondrial membrane with a molecular mass of 18 kDa. TSPO binds, such as the GABA A receptor benzodiazepine.

Among many other functions, it is involved in the regulation of the biosynthesis of steroid hormones, and porphyrins, and plays a role in apoptosis. TSTT in 1977 discovered when they sought in peripheral tissues by binding sites for diazepam.

The nucleotide sequence is highly conserved and encodes a membrane protein with five transmembrane helices likely. Homologous proteins are found in bacteria, plants and animals. A knockout mouse in which TSPO gene is switched off, dies in early embryonic stages. A knockout moss in one of these genes has been turned off is viable but vulnerable to stress.

Functions

There is evidence for at least two main functions of the TSTT: cholesterol - binding, followed by cholesterol transport, as well as Porphyrinbindung and transportation.

Steroidhormonbiosynthese

The polypeptide DBI ( diazepam binding inhibitor ) interacts with the TSTT and stimulates Pregnenolonbildung in the mitochondria. The biosynthesis of all steroid hormones and neurosteroids via pregnenolone. Other TSPO ligands also stimulate Steroidhormonbiosynthese and Neurosteroidbiosynthese. TSPO conveys the cholesterol transport from the outer to the inner membrane of the mitochondria. This leads to increased cholesterol metabolism. In the matrix of the mitochondria is the side-chain -cleaving enzyme, a cytochrome P450, which provides the elimination of cholesterol from Isocapronal pregnenolone.

Porphyrin transport and heme biosynthesis

In the mitochondria is also carried the heme biosynthesis. This gives TSPO import of precursor coproporphyrinogen III. From this via the intermediates protoporphyrinogen IX, protoporphyrin IX is formed by inserting the central iron ion in the heme of mitochondrial matrix.

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