title: Targeting mitochondrial energy metabolism with TSPO ligands.
abstract: The translocator protein (18 kDa) (TSPO) resides on the outer mitochondrial membrane where it is believed to participate in cholesterol transport and steroid hormone synthesis. Although it is almost ubiquitously expressed, what TSPO does in non-steroidogenic tissues is largely unexplored. Recent studies report changes in glucose homoeostasis and cellular energy production when TSPO function is modulated by selective ligands or by genetic loss-of-function. This review summarizes findings that connect TSPO function with the regulation of mitochondrial energy metabolism. The juxtaposition of TSPO at the cytosolic/mitochondrial interface and the existence of endogenous ligands that are regulated by metabolism suggest that TSPO functions to adapt mitochondrial to cellular metabolism. From a pharmacological perspective the specific up-regulation of TSPO in neuro-inflammatory and injury-induced conditions make TSPO an interesting, druggable target of mitochondrial metabolism.
authors.affiliation: Nestlé Institute of Health Sciences, EPFL Innovation Park, Bâtiment H, 1015 Lausanne, Switzerland Philipp.Gut@rd.nestle.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Gut
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008024:Ligands; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: PK 11195; diabetes mellitus; metabolic disease; mitochondria; mitochondrial drugs; zebrafish