title: TSPO is a REDOX regulator of cell mitophagy.
abstract: The mitochondrial 18-kDa translocator protein (TSPO) was originally discovered as a peripheral binding site of benzodiazepines to be later described as a core element of cholesterol trafficking between cytosol and mitochondria from which the current nomenclature originated. The high affinity it exhibits with chemicals (i.e. PK11195) has generated interest in the development of mitochondrial based TSPO-binding drugs for in vitro and in vivo analysis. Increased TSPO expression is observed in numerous pathologies such as cancer and inflammatory conditions of the central nervous system (CNS) that have been successfully exploited via protocols of positron emission tomography (PET) imaging. We endeavoured to dissect the molecular role of TSPO in mitochondrial cell biology and discovered a functional link with quality control mechanisms operated by selective autophagy. This review focuses on the current understanding of this pathway and focuses on the interplay with reactive oxygen species (ROS) and the voltage-dependent anion channel (VDAC), to which TSPO binds, in the regulation of cell mitophagy and hence homoeostasis of the mitochondrial network as a whole.
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London NW1 0TU, U.K.
authors.forename: Jemma
authors.initials: J
authors.lastname: Gatliff
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London NW1 0TU, U.K. University College London Consortium for Mitochondrial Research, Royal College, London WC1 6BT, U.K. mcampanella@rvc.ac.uk.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Campanella
mesh_terms: D006801:Humans; D063306:Mitophagy; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D018079:Receptors, GABA; C499229:TSPO protein, human; D050994:Voltage-Dependent Anion Channels
keywords: autophagy; mitochondria; translocator protein (TSPO); voltage-dependent anion channel 1 (VDAC1) and reactive oxygen species (ROS)