Insulin resistance and many metabolic disorders are causally linked to mitochondrial dysfunction or defective mitochondrial quality control. Mitophagy is a highly selective mechanism that recognizes and removes damaged mitochondria to maintain mitochondrial homeostasis . Here, we addressed the potential role of FUNDC1 , a mediator of mitophagy, in pancreatic β-cell dysfunction under lipotoxicity . In pancreatic MIN6 cells, FUNDC1 deficiency aggravated palmitate-induced mitochondrial dysfunction, which led to cell death and insulin insensitivity . Interestingly, FUNDC1 overexpression prevented these cellular harms brought on by palmitate. In mice models, pancreatic-specific FUNDC1 overexpression alleviated high-fat diet (HFD)-induced insulin resistance and obesity. Mechanistically, pancreatic-specific overexpression of FUNDC1 ameliorated mitochondrial defects and endoplasmic reticulum (ER) stress upon HFD. Our research indicates that FUNDC1 plays an essential role in apoptosis and dysfunction of pancreatic β-cells via modulating lipotoxicity-induced mitochondrial defects.
Home>FUNDC1 modulates mitochondrial defects and pancreatic β-cell dysfunction under lipotoxicity
FUNDC1 modulates mitochondrial defects and pancreatic β-cell dysfunction under lipotoxicity
- Impact factors: 3.1
- Publication: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Author:Beier Tong, Zhengwei Zhang, Xuefeng Li, Jie Liu, Huawei Wang, Linyang Song, Jieyuan Feng, Zhe Dai, Yancheng Xu
- DOI citation-doi:10.1016/j.bbrc.2023.06.042
- Date:2023-06-14