RT info:eu-repo/semantics/article T1 Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis A1 Peña Cearra, Ainize A1 Pascual Itoiz, Miguel Ángel A1 Lavín, José Luis A1 Fuertes Franco, Miguel A1 Martín Ruiz, Itziar A1 Castelo, Janire A1 Palacios, Ainhoa A1 Barriales, Diego A1 Fullaondo, Asier A1 Aransay, Ana M. A1 Rodriguez, Héctor A1 Anguita, Juan A1 Abecia, Leticia A2 Sanidad Animal K1 Biología K1 Inmunología K1 Medicina. Salud K1 Sanidad animal K1 Immunology K1 Microbiology K1 2412 Inmunología K1 3109.03 Inmunología K1 2414 Microbiología K1 3109.05 Microbiología AB [EN]Inflammatory bowel disease (IBD) is a complex, chronic, relapsing and heterogeneous disease induced by environmental, genomic, microbial and immunological factors. MCJ is a mitochondrial protein that regulates the metabolic status of macrophages and their response to translocated bacteria. Previously, an acute murine model of DSS-induced colitis showed increased disease severity due to MCJ deficiency. Unexpectedly, we now show that MCJ-deficient mice have augmented tumor necrosis factor α converting enzyme (TACE) activity in the context of chronic inflammation. This adaptative change likely affects the balance between soluble and transmembrane TNF and supports the association of the soluble form and a milder phenotype. Interestingly, the general shifts in microbial composition previously observed during acute inflammation were absent in the chronic model of inflammation in MCJ-deficient mice. However, the lack of the mitochondrial protein resulted in increased alpha diversity and the reduction in critical microbial members associated with inflammation, such as Ruminococcus gnavus, which could be associated with TACE activity. These results provide evidence of the dynamic metabolic adaptation of the colon tissue to chronic inflammatory changes mediated by the control of mitochondrial function. PB Nature Research LK https://hdl.handle.net/10612/18806 UL https://hdl.handle.net/10612/18806 NO Peña-Cearra, A., Pascual-Itoiz, M. A., Lavín, J. L., Fuertes, M., Martín-Ruiz, I., Castelo, J., Palacios, A., Barriales, D., Fullaondo, A., Aransay, A. M., Rodríguez, H., Anguita, J., & Abecia, L. (2022). Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis. Scientific Reports, 12(1). https://doi.org/10.1038/S41598-022-13480-Y DS BULERIA. Repositorio Institucional de la Universidad de León RD 23-may-2024