IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.

Title

IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.

Creator

Zhou H; Wang H; Yu M; Schugar RC; Qian W; Tang F; Liu W; Yang H; McDowell RE; Zhao J; Gao J; Dongre A; Carman JA; Yin M; Drazba JA; Dent R; Hine C; Chen Y; Smith JD; Fox PL; Brown JM; Li X

Publisher

Nature Immunology

Date

2020
2020-08-10

Description

Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of IRAK2 Myddosome to mitochondria outer membranes via recognition by TOM20, followed by TIMM50-guided translocation of IRAK2 into mitochondria inner membranes, to suppress oxidative phosphorylation and fatty acid oxidation, thereby attenuating energy expenditure. Adipocyte-specific MyD88 or IRAK2 deficiency reduced high-fat-diet-induced weight gain, increased energy expenditure and ameliorated insulin resistance, associated with a smaller adipocyte size and increased cristae formation. IRAK2 kinase inactivation also reduced high-fat diet-induced metabolic diseases. Mechanistically, IRAK2 suppressed respiratory super-complex formation via interaction with PHB1 and OPA1 upon stimulation of IL-1. Taken together, our results suggest that the IRAK2 Myddosome functions as a critical link between inflammation and metabolism, representing a novel therapeutic target for patients with obesity.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1529-2916 1529-2908

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences

Update Year & Number

August 2020 List

Citation

Zhou H; Wang H; Yu M; Schugar RC; Qian W; Tang F; Liu W; Yang H; McDowell RE; Zhao J; Gao J; Dongre A; Carman JA; Yin M; Drazba JA; Dent R; Hine C; Chen Y; Smith JD; Fox PL; Brown JM; Li X, “IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.,” NEOMED Bibliography Database, accessed December 1, 2021, https://neomed.omeka.net/items/show/11230.

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