Jul 5, 2018

Insufficient autophagy: a novel autophagic flux scenario uncovered by impaired liver TFEB-mediated lysosomal biogenesis from chronic alcohol-drinking mice

Autophagy
Xiaojuan ChaoWen-Xing Ding

Abstract

Macroautophagy/autophagy is a dynamic process, and newly synthesized autophagosomes need to fuse with lysosomes to complete the full process, which is referred to as autophagic degradation or autophagic flux. Therefore, the proper number and function of lysosomes are critical for accomplishing autophagic flux. In a recent study, we found that chronic ethanol consumption impairs TFEB (transcription factor EB) function, which leads to decreased lysosomal biogenesis resulting in hepatic steatosis and liver injury in mice. Interestingly, using the autophagic flux assay recommended by the autophagy guidelines, we discovered a novel autophagic flux scenario, which we termed insufficient autophagy. Insufficient autophagy is a scenario in which cells have a decreased number of lysosomes resulting in the accumulation of early autophagosomes. Insufficient autophagy is marked by a partially increased autophagic flux, but the process cannot reach its full degradative capacity due to the lack of a sufficient number of lysosomes. Our work demonstrated that pharmacological or genetic activation of TFEB-mediated lysosomal biogenesis enhances autophagic flux coupled with mitochondrial biogenesis in protecting against ethanol-induced liver injur...Continue Reading

  • References1
  • Citations3

Mentioned in this Paper

Study
Ethanol
TFEB
Ethanol Measurement
Tfeb
Fatty Liver
Vacuolar Myopathy
Alcoholic Intoxication, Chronic
TFEB protein, human
Macroautophagy

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