TSPO, reactive oxygen species and oxidative stress in physiological and pathological situations: a complex relationship

Since its discovery in 1977 in the external membrane of mitochondria, the precise role of TSPO, previously named PBR for peripheral type benzodiazepine receptor, remains an enigma because of its interactions with various exogenous and endogenous ligands such as cholesterol, porphyrins and its implication in different cellular processes. Moreover, its presence in organisms ranging from bacteria to humans and its wide distribution in the body, including central nervous system, asked the question of its conserved function. Its involvement in many diseases often connected to inflammation led to the development of many positrons emission tomography tracers, but also questioned its link to the production of reactive oxygen species (ROS) well described in the inflammation processes. This critical review presents the various systems involving TSPO that produce ROS, such as for instance the respiratory chain or the NADPH oxidases. The protein partners that have been described to interact with TSPO in such processes are also presented. Finally, the relationships of TSPO with diseases implicating ROS are overviewed.