The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis - Archive ouverte HAL Access content directly
Journal Articles Scientific Reports Year : 2020

The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis

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Miguel Angel Pascual-Itoiz
Ainize Peña-Cearra
  • Function : Author
Itziar Martín-Ruiz
  • Function : Author
José Luis Lavín
  • Function : Author
Carolina Simó
  • Function : Author
Héctor Rodríguez
  • Function : Author
Estibaliz Atondo
  • Function : Author
Juana María Flores
  • Function : Author
Ana Carreras-González
  • Function : Author
Julen Tomás-Cortázar
  • Function : Author
Diego Barriales
Ainhoa Palacios
  • Function : Author
Aize Pellón
Asier Fullaondo
  • Function : Author
Rafael Prados-Rosales
  • Function : Author
Juan Anguita
Leticia Abecia
  • Function : Author

Abstract

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.

Dates and versions

hal-03793774 , version 1 (01-10-2022)

Licence

Attribution - CC BY 4.0

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Cite

Miguel Angel Pascual-Itoiz, Ainize Peña-Cearra, Itziar Martín-Ruiz, José Luis Lavín, Carolina Simó, et al.. The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis. Scientific Reports, 2020, 10 (1), pp.572. ⟨10.1038/s41598-019-57348-0⟩. ⟨hal-03793774⟩
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