Molecular and Cellular Mechanisms Responsible for Cellular Stress and Low-grade Inflammation Induced by a Super-low Dose of Endotoxin

• DOI: 10.1074/jbc.m114.569210
• Publication Date: 2014-04-24T01:29:55Z
• Authors: Bianca Baker; Urmila Maitra; Shuo Geng; Liwu Li
• Keywords: Dephosphorylation; MFN1

Super-low-dose endotoxemia in experimental animals and humans is linked to low-grade chronic inflammatory diseases. However, the underlying molecular cellular mechanisms are not well understood. In this study, we examined effects of a super-low dose LPS on inflammation macrophages as mechanisms. We observed that induces mitochondrial fission cell necroptosis primary murine macrophages, dependent upon interleukin 1 receptor-associated kinase (IRAK-1). Mechanistically, our study reveals causes protein ubiquitination degradation mitofusin (Mfn1), molecule required for maintaining proper fusion. A also leads dephosphorylation activation Drp1, responsible necroptosis. Furthermore, demonstrated activates receptor interacting 3 (RIP3), key critical assembly necrosome complex, initiation Drp1 dephosphorylation, The abolished harvested from IRAK-1-deficient mice. Taken together, identified novel pathway stress challenged with endotoxin. This may reconcile often associated endotoxemia.