Fig. 6

The molecular mechanism of autophagy and its relationship with MAFLD. (1) Under normal conditions, mTORC1 phosphorylates and combines with ULK1/2, mAtg13 protein and FIP200 protein to form a functional silencing complex. When ER stress, oxidative stress, etc. activate autophagy, the functional silencing complex dissociates, and autophagosomes begin to recruit Atg protein, ULK1/2, mAtg13 and FIP200, to form a functional complex. (2) The autophagy-inducing complexes PtdIns3K class III, hVps34, Beclin1, and P150 are transported to the ER through microtubules to begin autophagic nucleation to induce the formation of restricted membranes. (3) Two ubiquitin-like conjugation systems, Atg12-Atg5-Atg16 L and PE/LC3, form a complex and participate in membrane elongation and isolate membrane-formation events to finally close into a double-layer membrane vesicle structure. (4) The fusion of autophagosomes and lysosomes leads to cargo degradation. The degraded products (amino acids, etc.) are then released into the cytosol through the lysosomal membrane permease, which produces a subsequent response that may be related to MAFLD-induced lipid accumulation, fibrosis and inflammation