Figure 2.

The autophagy machinery and targetable autophagic pathway proteins. Autophagy is a metabolic process of cellular self-digestion in which cellular components, such as abnormal protein aggregates and damaged organelles, serve as recycling substrates in order to generate energy or metabolic precursors, often in response to external stress. The process starts with phagophore initiation, which is regulated by ULK1 and VPS34 complexes, which can be blocked by selective inhibitors, as indicated, as well as ATG activity, resulting in the initiation and elongation of the phagophore membrane. Processing of LC3 by ATG4b as well as several ATGs leads to maturation and finally completion of the autophagosome. The autophagosome then fuses with the lysosome, a step that can be pharmacologically blocked with chloroquine or other compounds, as indicated. In the resulting autophagolysosome, the pH drops to <5, leading to degradation of its collected components.