Mitochondrial dysfunction regulates the JAK/STAT pathway by LKB1-mediated AMPK activation in an ER stress-independent manner.

Mitochondrial dysfunction regulates the JAK/STAT pathway by LKB1-mediated AMPK activation in an ER stress-independent manner. Biochem Cell Biol. 2019 May 09;: Authors: Kim DY, Lim SG, Suk K, Lee WH Abstract Mitochondria affect cellular functions alone or in cooperation with other cellular organelles. Recent research has demonstrated the close relationship of mitochondria with the endoplasmic reticulum (ER), both at the physical and the functional level. In an effort to define the combined effect mitochondrial dysfunction (MD) and ER stress in the proinflammatory activities of macrophages, the human macrophage-like monocytic leukemia cell line THP-1 was treated with mitochondrial electron transport chain (ETC) blockers, and changes in the cellular responses upon stimulation by interferon (IFN)-γ were analyzed. Induction of mitochondrial dysfunction (MD) with ETC blockers resulted in suppression of IFN-induced activation of JAK1 and STAT1/3, as well as the expression of STAT1-regulated genes. In addition, experiments utilizing pharmacological modulators of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and liver kinase B1 (LKB1)-deficient HeLa cells demonstrated that these suppressive effects are mediated by the LKB1/AMPK pathway. Treatment with pharmacological inhibitors of ER stress sensors failed to affect these processes, thus indicating that involvement of ER stress is not required. These results indicate that M...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research