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

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 com

SUBMITTER: Pascual-Itoiz MA 

PROVIDER: S-EPMC6969106 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature