Premium
TAK1 Inhibition Elicits Mitochondrial ROS to Block Intracellular Bacterial Colonization
Author(s) -
LópezPérez Wilfred,
Sai Kazuhito,
Sakamachi Yosuke,
Parsons Cameron,
Kathariou Sophia,
NinomiyaTsuji Jun
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.00201
Subject(s) - intracellular , microbiology and biotechnology , effector , protein kinase a , reactive oxygen species , kinase , biology , signal transduction , chemistry
Mitogen activated protein kinase kinase kinase 7 (MAP3K7), known as TAK1, is an intracellular signaling intermediate of inflammatory responses. However, a series of mouse Tak1 gene deletion analysis has revealed that ablation of TAK1 does not prevent but rather elicits inflammation, which is accompanied by elevation of reactive oxygen species (ROS). These have been considered as consequences of non‐physiological loss of TAK1. Contrary to this view, here we propose that TAK1 inhibition‐induced ROS are an active cellular process that targets intracellular bacteria. Intracellular bacterial effector proteins such as Yersinia's outer membrane protein YopJ are known to inhibit TAK1 to circumvent the inflammatory host responses. We found that such TAK1 inhibition particularly induces mitochondrial‐derived ROS, which effectively destroys intracellular bacteria. Our results reveal a previously unrecognized host defense mechanism linking inhibition of inflammatory signaling with mitochondrial ROS.