title: Lost in translocation: the functions of the 18-kD translocator protein.
abstract: Research spanning nearly four decades has assigned to the translocator protein (18 kDa) (TSPO) a critical role, among others, in the mitochondrial import of cholesterol, the subsequent steps of (neuro)steroid production, and systemic endocrine regulation, with implications for the pathophysiology of immune, inflammatory, neurodegenerative, and psychiatric as well as neoplastic diseases. Recent knockout studies in mice unexpectedly report normal or latent phenotypes, raising doubts about the protein's role in steroidogenesis and other previously postulated functions and challenging the validity of earlier data on the selectivity of TSPO-binding drugs. Here we provide a synthesis of the current debate from a structural and molecular biology perspective, discuss the limits of inference in loss-of-function (gene knockout) studies, and suggest new functions of TSPO.
authors.affiliation: Nestlé Institute of Health Sciences, EPFL Innovation Park, Bâtiment H, 1015 Lausanne, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Gut
authors.affiliation: Max-Planck-Institut für Biophysikalische Chemie, 37077 Göttingen, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 37077 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37073 Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
authors.affiliation: Life Sciences, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia; National Imaging Facility and Ramaciotti Centre for Brain Imaging, Brain and Mind Research Institute, Faculty of Health Sciences, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: rib@ansto.gov.au.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism
chemical_list: C463819:Bzrp protein, mouse; D018079:Receptors, GABA; C499229:TSPO protein, human; D002784:Cholesterol
keywords: REV-ERBα; cholesterol; heme metabolism; mitochondrial permeability transition pore; neuroimaging; neuroinflammation; peripheral benzodiazepine receptor