Enigmatic Translocator protein (TSPO) and cellular stress regulation

Batoko, Henri; Veljanovski, Vasko; Jurkiewicz, Paweł

doi:10.1016/j.tibs.2015.07.001

Cited by 53 publications

(59 citation statements)

References 60 publications

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“…These antagonistic expectancies regarding properties of TSPO and its ligands potentially may lead to widely divergent discrepancies in research approaches and interpretations of results. Another confounding aspect does relate to the now well appreciated concept that TSPO has homeostatic functions [20,23,26,38,62,63,70,71]. Assuming this to be true, many of the seemingly contradictory results can be explained as upregulatory and downregulatory characteristics of this potential homeostatic apparatus.…”

Section: Discussionmentioning

confidence: 99%

Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Yasin

Veenman

Singh

et al. 2017

IJMS

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It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 min, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with real-time, reverse transcriptase (RT) PCR. At the time points of 15, 30, 45, and 60 min, as well as 3 and 24 h of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 h of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

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Section: Discussionmentioning

confidence: 99%

Classical and Novel TSPO Ligands for the Mitochondrial TSPO Can Modulate Nuclear Gene Expression: Implications for Mitochondrial Retrograde Signaling

Yasin

Veenman

Singh

et al. 2017

IJMS

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“…The Drosophila homolog of Jwa is required for ethanol tolerance (Li et al , 2008). TSPO (also called the peripheral benzodiazepine receptor) is a mitochondrial outer-membrane protein proposed to be involved in cellular stress regulation (Batoko et al , 2015). TSPO interacts with the diazepam binding inhibitor (DBI), which has been proposed to contribute to drug dependence.…”

Section: Classical Genetic Screens and Candidate Gene Analysismentioning

confidence: 99%

Genetics and genomics of alcohol responses in Drosophila

et al. 2017

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Drosophila melanogaster has become a significant model organism for alcohol research. In flies, a rich variety of behaviors can be leveraged for identifying genes affecting alcohol responses and adaptations. Furthermore, almost all genes can be easily genetically manipulated. Despite the great evolutionary distance between flies and mammals, many of the same genes have been implicated in strikingly similar alcohol-induced behaviors. A major problem in medical research today is that it is difficult to extrapolate from any single model system to humans. Strong evolutionary conservation of a mechanistic response between distantly related organisms, such as flies and mammals, is a powerful predictor that conservation will continue all the way to humans. This review describes the state of the Drosophila alcohol research field. It describes common alcohol behavioral assays, the independent origins of resistance and tolerance, the results of classical genetic screens and candidate gene analysis, and the outcomes of recent genomics studies employing GWAS, transcriptome, miRNA, and genome-wide histone acetylation surveys.

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“…Aunque algunas funciones celulares de la TSPO se han conservado, como el transporte de colesterol, su significancia biológica parece estar adaptada para funciones específicas críticas en algunos tejidos (35).…”

Section: Proteína Translocadora Mitocondrial (Tspo) 18 Kdaunclassified