The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.
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January 2016
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Showing TSPO transcriptional regulation cross-talk between hormone- and redox-sensitive signal transduction pathways. Courtesy of J. Gatliff and M. Campanella (see pages 107–121 for further details). - PDF Icon PDF LinkFront Matter
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Review Article|
January 05 2016
TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria
Jemma Gatliff;
Jemma Gatliff
*Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street NW1 0TU, London, U.K.
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Michelangelo Campanella
Michelangelo Campanella
1
*Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street NW1 0TU, London, U.K.
†University College London Consortium for Mitochondrial Research, Gower Street WC1 6BT, London, United Kingdom
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 13 2015
Revision Received:
October 07 2015
Accepted:
October 21 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (2): 107–121.
Article history
Received:
August 13 2015
Revision Received:
October 07 2015
Accepted:
October 21 2015
Citation
Jemma Gatliff, Michelangelo Campanella; TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria. Biochem J 15 January 2016; 473 (2): 107–121. doi: https://doi.org/10.1042/BJ20150899
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