title: Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells.
abstract: 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.
  
  
  CONCLUSIONS
  This work implicates TSPO in the maintenance of mitochondrial membrane integrity and in the control of mitochondrial ROS production, ultimately favoring tissue regeneration.
authors.affiliation: Sorbonne Universités - Université Pierre et Marie Curie Université de Paris VI, École Normale Supérieure - PSL Research University, Département de Chimie, CNRS UMR 7203 LBM, 4 Place Jussieu, F-75005, Paris, France.|The Research Institute of the McGill University Health Center and the Department of Medicine, McGill University, Montreal, Quebec, H4A 3J1, Canada.
authors.forename: Leeyah
authors.initials: L
authors.lastname: Issop
authors.affiliation: INSERM UMRS 1134, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, Université Paris 7 Denis Diderot, F-75015 Paris, France.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Ostuni
authors.affiliation: The Research Institute of the McGill University Health Center and the Department of Medicine, McGill University, Montreal, Quebec, H4A 3J1, Canada.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: CNRS FR 3636, Université Paris Descartes, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Laforge
authors.affiliation: Sorbonne Universités - Université Pierre et Marie Curie Université de Paris VI, École Normale Supérieure - PSL Research University, Département de Chimie, CNRS UMR 7203 LBM, 4 Place Jussieu, F-75005, Paris, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Péranzi
authors.affiliation: INSERM UMR 1141, Hôpital Robert Debré, and Université Paris 7 Denis Diderot, F-75019, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.affiliation: INSERM UMR 1141, Hôpital Robert Debré, and Université Paris 7 Denis Diderot, F-75019, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Benoist
authors.affiliation: CNRS FR 3636, Université Paris Descartes, Paris, France.|Université Laval, Faculté de Médecine, Département de microbiologie-infectiologie et d'immunologie, Quebec City, Quebec, G1V06A, Canada.
authors.forename: Jérome
authors.initials: J
authors.lastname: Estaquier
authors.affiliation: The Research Institute of the McGill University Health Center and the Department of Medicine, McGill University, Montreal, Quebec, H4A 3J1, Canada.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
authors.affiliation: Sorbonne Universités - Université Pierre et Marie Curie Université de Paris VI, École Normale Supérieure - PSL Research University, Département de Chimie, CNRS UMR 7203 LBM, 4 Place Jussieu, F-75005, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lacapère
mesh_terms: D016923:Cell Death; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018079:Receptors, GABA / Q000096:biosynthesis*; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000494:pharmacology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D018079:Receptors, GABA; C499229:TSPO protein, human; D014409:Tumor Necrosis Factor-alpha