Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome
Hao Wu, You Wang, Wenhui Li, Hui Chen, Lei Du, Dong Liu, Xiaohui Wang, Tao Xu, Lei Liu & Quan Chen
Abstract
There is overwhelming evidence for an association between impaired mitochondrial function and metabolic syndrome. Mitophagy, a process that selectively removes damaged mitochondriaviaa specialized form of autophagy, is essential for mitochondrial quality control (mitochondrial QC) and metabolic homeostasis. We thus addressed the potential role of defective mitophagy in the pathogenesis of metabolic disorders. Mice lackingFundc1, a newly characterized mitophagy receptor, develop more severe obesity and insulin resistance when fed a high-fat diet (HFD). Ablation ofFundc1results in defective mitophagy and impaired mitochondrial QC in vitro and in white adipose tissue (WAT). In addition, there is more pronounced WAT remodeling with more adipose tissue-associated macrophages infiltration, more M1 macrophage polarization and thus an elevated inflammatory response. Mechanistically, hyperactivation of MAPK/JNK leads to insulin insensitivity, which can be inhibited by knocking outMapk8/Jnk1infundc1KO mice. Our results demonstrate that dysregulated mitochondrial QC due to defective mitophagy receptor FUNDC1 links with metabolic disorders via MAPK signaling and inflammatory responses.
附件下载：
Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome,Autophagy, 06 Apr 2019
Autophagy, 06 April, 2019， DOI:http://dx.doi.org/10.1080/15548627.2019.1596482
Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome
Hao Wu, You Wang, Wenhui Li, Hui Chen, Lei Du, Dong Liu, Xiaohui Wang, Tao Xu, Lei Liu & Quan Chen
Abstract
There is overwhelming evidence for an association between impaired mitochondrial function and metabolic syndrome. Mitophagy, a process that selectively removes damaged mitochondriaviaa specialized form of autophagy, is essential for mitochondrial quality control (mitochondrial QC) and metabolic homeostasis. We thus addressed the potential role of defective mitophagy in the pathogenesis of metabolic disorders. Mice lackingFundc1, a newly characterized mitophagy receptor, develop more severe obesity and insulin resistance when fed a high-fat diet (HFD). Ablation ofFundc1results in defective mitophagy and impaired mitochondrial QC in vitro and in white adipose tissue (WAT). In addition, there is more pronounced WAT remodeling with more adipose tissue-associated macrophages infiltration, more M1 macrophage polarization and thus an elevated inflammatory response. Mechanistically, hyperactivation of MAPK/JNK leads to insulin insensitivity, which can be inhibited by knocking outMapk8/Jnk1infundc1KO mice. Our results demonstrate that dysregulated mitochondrial QC due to defective mitophagy receptor FUNDC1 links with metabolic disorders via MAPK signaling and inflammatory responses.
文章链接：https://www.tandfonline.com/doi/full/10.1080/15548627.2019.1596482