Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells.
Τίτλος | Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Issop, L., Ostuni M. A., Lee S., Laforge M., Péranzi G., Rustin P., Benoist J-F., Estaquier J., Papadopoulos V., & Lacapère J-J. |
Journal | PLoS One |
Volume | 11 |
Issue | 4 |
Pagination | e0152919 |
Date Published | 2016 |
ISSN | 1932-6203 |
Λέξεις κλειδιά | Cell Death, Cell Line, Tumor, Colon, Colonic Neoplasms, Gene Expression Regulation, Neoplastic, Humans, Inflammation, Interleukin-8, Mitochondria, Mitochondrial Membranes, Neoplasm Proteins, Reactive Oxygen Species, Receptors, GABA, Stress, Physiological, Tumor Necrosis Factor-alpha |
Abstract | UNLABELLED: Chronic inflammation of the gastrointestinal tract increasing the risk of cancer has been described to be linked to the high expression of the mitochondrial translocator protein (18 kDa; TSPO). Accordingly, TSPO drug ligands have been shown to regulate cytokine production and to improve tissue reconstruction. We used HT-29 human colon carcinoma cells to evaluate the role of TSPO and its drug ligands in tumor necrosis factor (TNF)-induced inflammation. TNF-induced interleukin (IL)-8 expression, coupled to reactive oxygen species (ROS) production, was followed by TSPO overexpression. TNF also destabilized mitochondrial ultrastructure, inducing cell death by apoptosis. Treatment with the TSPO drug ligand PK 11195 maintained the mitochondrial ultrastructure, reducing IL-8 and ROS production and cell death. TSPO silencing and overexpression studies demonstrated that the presence of TSPO is essential to control IL-8 and ROS production, so as to maintain mitochondrial ultrastructure and to prevent cell death. Taken together, our data indicate that inflammation results in the disruption of mitochondrial complexes containing TSPO, leading to cell death and epithelia disruption.SIGNIFICANCE: This work implicates TSPO in the maintenance of mitochondrial membrane integrity and in the control of mitochondrial ROS production, ultimately favoring tissue regeneration. |
DOI | 10.1371/journal.pone.0152919 |
Alternate Journal | PLoS ONE |
PubMed ID | 27054921 |
PubMed Central ID | PMC4824355 |
Grant List | MOP-125983 / / Canadian Institutes of Health Research / Canada |