Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells

PLoS One

Vassilios Papadopoulos¹  Gabriel Péranzi¹  Jérome Estaquier²  Jean-François Benoist²  Sunghoon Lee³  Leeyah Issop⁴  Pierre Rustin⁴  Mireille Laforge⁵  Mariano A. Ostuni⁵  Jean-Jacques Lacapère⁶ 

[1] CNRS FR 3636, Université Paris Descartes, Paris, France;INSERM UMR 1141, Hôpital Robert Debré, and Université Paris 7 Denis Diderot, F-75019, Paris, France;INSERM UMRS 1134, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, Université Paris 7 Denis Diderot, F-75015 Paris, France;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;Université Laval, Faculté de Médecine, Département de microbiologie-infectiologie et d’immunologie, Quebec City, Quebec, G1V06A, Canada

关键词: Mitochondria;    Inflammation;    Apoptosis;    Mitochondrial membrane;    Cytokines;    Inflammatory bowel disease;    Colon;    Secretion;   

DOI  :  10.1371/journal.pone.0152919

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY