Figure 1.

Principal functions of the 18-kDa translocator protein (TSPO): initiation of programmed cell death, including apoptosis, as well as regulation of the cell’s nuclear gene expression. This figure presents an overview of the cellular pathways influenced by TSPO. TSPO favors neurosteroid synthesis by transporting cholesterol over the outer mitochondrial membrane to the inner mitochondrial membrane. Furthermore, it modulates ATP synthase activity, thus initiating reactive oxygen species (ROS) production, which can result in cardiolipin oxidation and opening of the mitochondrial permeability transition pore (mPTP). Opening of the mPTP allows for ATP and Ca²⁺ release, and depolarization of the mitochondrial membrane. This depolarization results in opening of the Bax/Bak channel, allowing for the passage of cytochrome c into the cytosol as an initiating step for the mitochondrial apoptosis cascade. The mitochondrial ROS generation and ATP and Ca²⁺ release are also considered part of the mitochondria-to-nucleus pathway of cell nuclear gene expression modulation, which includes the modulation of hundreds to thousands of genes (see also [8,11,12,13]).