title: Translocator protein: pharmacology and steroidogenesis.
abstract: The translocator protein (TSPO; 18k Da) is an evolutionarily conserved outer mitochondrial membrane (OMM) protein highly expressed in steroid-synthesizing cells and found to possess a number of physiological and drug-binding partners. Extensive pharmacological, biochemical and cell biological research over the years has led to a model of TSPO involvement in mitochondrial cholesterol transport and promotion of steroid synthesis, a model guiding the design of drugs useful in stimulating neurosteroid synthesis and alleviating psychopathological symptoms. The involvement of TSPO in these processes has been called into question; however, with the publication of TSPO-deletion mouse models which saw no changes in steroid production. Here, we review work characterizing TSPO in steroidogenesis and offer perspective to research into TSPO pharmacology and its involvement in steroid biosynthesis.
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada Department of Medicine, McGill University, Montreal, Quebec H4A 3J1, Canada andrew.midzak@mail.mcgill.ca vassilios.papadopoulos@mcgill.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Midzak
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, U.S.A.
authors.forename: Barry
authors.initials: B
authors.lastname: Zirkin
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada Department of Medicine, McGill University, Montreal, Quebec H4A 3J1, Canada Departments of Biochemistry and Pharmacology & Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada andrew.midzak@mail.mcgill.ca vassilios.papadopoulos@mcgill.ca.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D007546:Isoquinolines; D008024:Ligands; D018079:Receptors, GABA; D013256:Steroids; C499229:TSPO protein, human; D001569:Benzodiazepines; D002784:Cholesterol
keywords: 14-3-3 proteins; adrenal; aging; brain; cholesterol; gonads; hypercortisolism; hypogonadism; mitochondria; steroidogenesis; translocator protein (TSPO); voltage-dependent anion channel (VDAC)