The mitochondrial 18 kDa Translocator Protein (TSPO) was first detected by its capability to bind
benzodiazepines in peripheral tissues and later also in glial cells in the brain, hence its previous most common
name peripheral benzodiazepine receptor (PBR). TSPO has been implicated in various functions, including
apoptosis and steroidogenesis, among others. Various endogenous TSPO ligands have been proposed, for
example: Diazepam Binding Inhibitor (DBI), triakontatetraneuropeptide (TTN), phospholipase A2 (PLA2), and
protoporphyrin IX. However, the functional implications of interactions between the TSPO and its putative
endogenous ligands still have to be firmly established. The TSPO has been suggested to interact with a
mitochondrial protein complex, summarized as mitochondrial membrane permeability transition pore (MPTP),
which is considered to regulate the mitochondrial membrane potential (ΔΨm). In addition, the TSPO is
associated with several other proteins. The associations of the TSPO with these various proteins at the
mitochondrial membranes have been attributed to functions such as apoptosis, steroidogenesis,
phosphorylation, reactive oxygen species (ROS) generation, ATP production, and collapse of the ΔΨm.
Interestingly, while TSPO is known to play a role in the modulation of steroid production, in turn, steroids are
also known to affect TSPO expression. As with the putative endogenous TSPO ligands, the effects of steroids
on TSPO functions still have to be established. In any case, steroid – TSPO interactions occur in organs and
tissues as diverse as the reproductive system, kidney, and brain. In general, the steroid – TSPO interactions
are thought to be part of stress responses, but may also be essential for reproductive events, embryonic
development, and responses to injury, including brain injury. The present review focuses on the role of TSPO
in cell death i.e. the notion that enhanced expression and / or activation of the TSPO leads to cell death, and
the potential of steroids to regulate TSPO expression and activation.
Adenine nucleotide transporter (ANT), Bcl2, brain trauma, cholesterol, creatine kinase, cyclophylin D,
hexokinase, voltage dependent anion channel (VDAC)
Department of Molecular Pharmacology, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, P.O. Box 9649, Bat-Galim, Haifa 31096, Israel.