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Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox Interaction in Colitis-Induced Mice

Title
Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox Interaction in Colitis-Induced Mice
Author
김재성
Keywords
Rubicon; p22phox; mitochondria; reactive oxygen species; colitis
Issue Date
2021-12
Publisher
MDPI
Citation
ANTIOXIDANTS; DEC 2021, 10 12, p1954 22p.
Abstract
The run/cysteine-rich-domain-containing Beclin1-interacting autophagy protein (Rubicon) is essential for the regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by interacting with p22phox to trigger the production of reactive oxygen species (ROS) in immune cells. In a previous study, we demonstrated that the interaction of Rubicon with p22phox increases cellular ROS levels. The correlation between Rubicon and mitochondrial ROS (mtROS) is poorly understood. Here, we report that Rubicon interacts with p22phox in the outer mitochondrial membrane in macrophages and patients with human ulcerative colitis. Upon lipopolysaccharide (LPS) activation, the binding of Rubicon to p22phox was elevated, and increased not only cellular ROS levels but also mtROS, with an impairment of mitochondrial complex III and mitochondrial biogenesis in macrophages. Furthermore, increased Rubicon decreases itochondrial metabolic flux in macrophages. Mito-TIPTP, which is a p22phox inhibitor containing a mitochondrial translocation signal, enhances mitochondrial function by inhibiting the association between Rubicon and p22phox in LPS-primed bone-marrow-derived macrophages (BMDMs) treated with adenosine riphosphate (ATP) or dextran sulfate sodium (DSS). Remarkably, Mito-TIPTP exhibited a therapeutic effect by decreasing mtROS in DSS-induced acute or chronic colitis mouse models. Thus, our findings suggest that Mito-TIPTP is a potential therapeutic agent for colitis by inhibiting the interaction between Rubicon and p22phox to recover mitochondrial function.
URI
https://www.proquest.com/docview/2612727936?accountid=11283https://repository.hanyang.ac.kr/handle/20.500.11754/169162
ISSN
20763921
DOI
10.3390/antiox10121954
Appears in Collections:
RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF NATURAL SCIENCE AND TECHNOLOGY(이학기술연구소) > Articles
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