Fig. 3

Schematic representation of cellular stresses in NAFLD. ER stress increases lipid droplet accumulation by activating factors involved in lipogenesis. IRGM plays an important role in increasing lipophagy of LDs. IRGM promotes lipophagy through complex formation with ULK1 and Beclin, binding to ATG16L1, and stimulation by Sirt1. Moreover, enhanced FFA β-oxidation in mitochondria by production of large amounts of ROS leads to a disruption of the electron transport chain. This defect leads to the leakage of e-, which immediately combines with oxygen to generate the superoxide anion radical, which is then converted to H₂O₂ by SOD2 activity. The antioxidant enzymes GPX1 and catalase convert H₂O₂ into H₂O and O₂. On the other hand, ER stress leads to mitochondrial damage by causing oxidative stress. IRGM regulates mitofilin stability during mitochondrial depolarization, leading to PINK1-Parkin-dependent ubiquitination and removal of defective mitochondria