TFEB and MLRO in hepatocyte dedifferentiation and alcohol-associated hepatitis (AH) and metabolic dysfunction-associated steatohepatitis (MASH). (IMAGE)
Caption
(A) The images show MLRO in primary cultured mouse hepatocytes. The bar scale is 500 nm. (B) The proposed model illustrates how lysosomes and TFEB regulate MLRO in hepatocyte dedifferentiation. Increased amino acid levels from lysosomal degradation promote mTOR translocation to the lysosomal membrane through the ‘Ragulator’ complex, leading to mTOR activation. This, in turn, phosphorylates TFEB, causing TFEB cytosolic retention and inactivation. When amino acid levels from lysosomal degradation are low, mTOR is inactivated, leading to decreased TFEB phosphorylation and increased nuclear TFEB translocation. TFEB then binds to Coordinated Lysosomal Expression and Regulation (CLEAR) motif-containing target genes involved in autophagy and lysosomal biogenesis. TFEB-mediated lysosomal biogenesis promotes the clearance of MLRO, inhibits hepatocyte dedifferentiation and attenuates the pathogenesis of AH and MASH. Figure 2B was generated using BioRender. MLRO, mitochondria-lysosome-related organelle; TFEB, transcription factor EB.
Credit
By Xiaowen Ma, Hong-Min Ni and Wen-Xing Ding
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Credit must be given to the creator. Only noncommercial uses of the work are permitted.
License
CC BY-NC