Fig. 1.

Regulation of autophagy by TFEB. In response to the loss of extracellular nutrients by starvation, there is decreased intracellular ERK1/2 activity. The reduction in ERK1/2 leads to dephosphorylation of cytosolic TFEB at Ser142. Dephosphorylation at this site allows nuclear translocation of TFEB where it increases transcription for a number of CLEAR network genes that encode for critical autophagic and lysosomal proteins. The increase in these proteins promotes autophagosome formation and lysosomal biogenesis to increase levels of autophagy.