The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis.,Scientific Reports

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The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41598-019-57348-0
Miguel Angel Pascual-Itoiz ₁ , Ainize Peña-Cearra _{1,

2} , Itziar Martín-Ruiz ₁ , José Luis Lavín ₁ , Carolina Simó ₃ , Héctor Rodríguez ₁ , Estibaliz Atondo ₁ , Juana María Flores ₄ , Ana Carreras-González ₁ , Julen Tomás-Cortázar ₁ , Diego Barriales ₁ , Ainhoa Palacios ₁ , Virginia García-Cañas ₃ , Aize Pellón ₁ , Asier Fullaondo ₂ , Ana Mª Aransay _{1,

5} , Rafael Prados-Rosales ₁ , Rebeca Martín ₆ , Juan Anguita _{1,

7} , Leticia Abecia ₁

Affiliation

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.

中文翻译：

线粒体负调节剂MCJ调节溃疡性结肠炎期间微生物群与宿主之间的相互作用。

最近的证据表明，在活动性溃疡性结肠炎（UC）患者中线粒体基因和功能降低，特别是电子传输链的复合物I的活性受到严重损害。MCJ是线粒体内膜蛋白，被认为是呼吸链复合物I的天然抑制剂。MCJ缺陷小鼠中实验性结肠炎的诱导导致Timp3表达上调，从而导致TACE活性受到抑制，从而可能抑制Tnf和Tnfr1脱落。结肠中的细胞膜。缺乏MCJ的小鼠还显示Myd88和Tlr9的更高表达，促炎基因和疾病严重程度。有趣的是，MCJ的缺乏导致了独特的微生物群代谢和组成，包括UC患者的肠道菌群-Ruminococcus gnavus。这些变化激发了对IgA水平的影响。UC患者的基因表达分析表明，MCJ的水平降低，TIMP3的表达更高，表明线粒体基因的作用与活动性UC之间的功能有关。MCJ缺乏会干扰宿主线粒体和微生物群之间的调节关系，从而影响疾病的严重程度。我们的结果表明线粒体功能可能是发病机理中的重要因素。所有人都支持UC期间MCJ监管的重要性。MCJ缺乏会干扰宿主线粒体和微生物群之间的调节关系，从而影响疾病的严重程度。我们的结果表明线粒体功能可能是发病机理中的重要因素。所有人都支持UC期间MCJ监管的重要性。MCJ缺乏会干扰宿主线粒体和微生物群之间的调节关系，从而影响疾病的严重程度。我们的结果表明线粒体功能可能是发病机理中的重要因素。所有人都支持UC期间MCJ监管的重要性。

更新日期：2020-01-17

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