The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis
2020
Pascual-Itoiz, Miguel Angel | Peña-Cearra, Ainize | Martín-Ruiz, Itziar | Lavín, José Luis | Simó, Carolina | Rodríguez, Héctor | Atondo, Estibaliz | Flores, Juana María | Carreras-González, Ana | Tomás-Cortázar, Julen | Barriales, Diego | Palacios, Ainhoa | García-Cañas, Virginia | Pellón, Aize | Fullaondo, Asier | Aransay, Ana Mª | Prados-Rosales, Rafael | Martín, Rebeca | Anguita, Juan | Abecia, Leticia | CIC BioGUNE ; CIC Spain | Instituto de Investigación en Ciencias de la Alimentación (CIAL) ; Consejo Superior de Investigaciones Cientificas = Spanish National Research Council (CSIC)-Universidad Autónoma de Madrid (UAM) | Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd) ; Liver Unit, Clínica Universitaria, CIBER-EHD | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
International audience
Показать больше [+] Меньше [-]Английский. Recent evidences indicate that mitochondrial genes and function are decreased in active ulcerative colitis (UC) patients, in particular, the activity of Complex I of the electron transport chain is heavily compromised. MCJ is a mitochondrial inner membrane protein identified as a natural inhibitor of respiratory chain Complex I. The induction of experimental colitis in MCJ-deficient mice leads to the upregulation of Timp3 expression resulting in the inhibition of TACE activity that likely inhibits Tnf and Tnfr1 shedding from the cell membrane in the colon. MCJ-deficient mice also show higher expression of Myd88 and Tlr9 , proinflammatory genes and disease severity. Interestingly, the absence of MCJ resulted in distinct microbiota metabolism and composition, including a member of the gut community in UC patients, Ruminococcus gnavus . These changes provoked an effect on IgA levels. Gene expression analyses in UC patients showed decreased levels of MCJ and higher expression of TIMP3 , suggesting a relevant role of mitochondrial genes and function among active UC. The MCJ deficiency disturbs the regulatory relationship between the host mitochondria and microbiota affecting disease severity. Our results indicate that mitochondria function may be an important factor in the pathogenesis. All together support the importance of MCJ regulation during UC.
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