Back
Full-text
Journal article

Lost in translocation: the functions of the 18-kD translocator protein.

  • Gut P Nestlé Institute of Health Sciences, EPFL Innovation Park, Bâtiment H, 1015 Lausanne, Switzerland.
  • Zweckstetter M 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.
  • Banati RB 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.
  • 2015-06-01
Published in:
  • Trends in endocrinology and metabolism: TEM. - 2015
REV-ERBα
cholesterol
heme metabolism
mitochondrial permeability transition pore
neuroimaging
neuroinflammation
peripheral benzodiazepine receptor
Animals
Cholesterol
Humans
Mitochondria
Receptors, GABA
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/112028
Statistics
Document views: 81 File downloads:
  • Full-text: 0