Mitoneet mediates TNFα-induced necroptosis promoted by exposure to fructose and ethanol.

ABSTRACT: Fructose and ethanol are metabolized principally in the liver and are both known to contribute to the development of hepatic steatosis that can progress to hepatic steatohepatitis. The present study indentifies a synergistic interaction between fructose and ethanol in promoting hepatocyte sensitivity to TNFα-induced necroptosis. Concurrent exposure to fructose and ethanol induces the overexpression of the CDGSH iron-sulfur domain-containing protein 1 (CISD1 or mitoneet), which is localized to the outer mitochondrial membrane. The increased expression of mitoneet primes the hepatocyte for TNFα-induced cytotoxicity. Treatment with TNFα induces the translocation of a Stat3-Grim-19 complex to the mitochondria, which binds to mitoneet and promotes the rapid release of its 2Fe-2S cluster, causin

SUBMITTER: Shulga N 

PROVIDER: S-EPMC3924205 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature