Figure 3.

Schematic depiction of autophagy activation in the context of trisomy

Upon activation via the ULK1 kinase, the phagophore membrane engulfs the cytoplasmic components to be degraded and fuses with lysosomes to enable degradation. mTORC1 kinase, a key nutrient sensor, regulates autophagosome assembly via inhibitory phosphorylations. Additionally, the transcription factors of the MIT/TFEB family, which are also mTORC1 targets, regulate the expression of autophagy- and lysosomal-specific genes. Autophagy is activated upon starvation, oxidative stress, unfolded protein response, or DNA damage via the cGAS/STING pathway.