Figure 3. Nutrient scavenging in PDA converges at the lysosome for breakdown of intracellular and extracellular cargo.

A) PDA cells show enhanced autophagy activation and macropinocytosis in vitro and in vivo. Autophagy involves formation of double membrane vesicles that surround a portion of cytoplasm thus encapsulating cargo material (protein, lipid, organelles) that is delivered to lytic organelles (lysosome) for breakdown. Positive (AMPK and VPS34) and negative (mTORC1) kinase regulators of autophagy are indicated. Macropinocytosis, the bulk uptake of extracellular material, occurs via plasma membrane invagination and generation of internalized macropinosomes. These cargo-laden vesicles similarly fuse with lysosomes for efficient degradation of the internalized material. Therefore lysosomes are a key central delivery port for substrates destined for breakdown and serve to recycle the constituent building blocks and support cellular metabolism. Drugs that modulate different aspects of these pathways are shown. B) Resident lysosomal enzymes, their substrates and final products are listed.