Proteolytic processing in autophagy

Autophagy is a catabolic process that regulates cell homeostasis by eliminating damaged whole organelles or macromolecules. The autophagic flow comprises the processes from the beginning of the autophagy to the degradation of the cargo, which allows the recycling of nutrients and obtaining basic building blocks in stressful situations. The proteolytic process is involved in the entire autophagic flow, with autophagy-related gene 4 family (ATG4s) and cathepsins being the key proteases for phagophore nucleation and cargo degradation, respectively. Changes in the activity or expression of ATG4s and cathepsins have been implicated in human diseases. On the other hand, caspases and calpains are negative regulators of autophagic flow, since these proteases degrade proteins essential for phagophore initiation and nucleation. In this chapter, an overview of the proteolytic process involved in autophagy is presented.