Human ATG4C knockout HEK-293T cell lysate

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

ATG4C also known as autophagin-3 is a cysteine protease involved in autophagy an important cellular degradation pathway. With a molecular mass of approximately 52 kDa the target plays a significant role in cytosolic processing. Primarily ATG4C acts in various tissues including the brain liver and muscle where it participates in the processing of essential autophagy-related proteins. The protein provides an enzymatic function necessary for the maturation and recycling of autophagosomes structures required for autophagy.

Biological function summary

ATG4C cleaves the ATG8 family proteins such as LC3 at a conserved glycine residue facilitating their conjugation to phosphatidylethanolamine. This step is critical in the elongation of the isolation membrane during autophagosome formation. ATG4C is not typically found as part of a large protein complex but its interaction with ATG8 family members is an important regulatory point. Its function in recycling ATG8-family proteins helps maintain cellular homeostasis and responds to stress conditions like nutrient deprivation.

Pathways

ATG4C plays a central role in the autophagy pathway essential for cell survival differentiation and tissue remodeling. The protein closely interacts with components of the autophagy machinery such as ATG5 and the ULK1 complex coordinating the effective sequestration of cytoplasmic constituents. Its activity impacts the broader cellular pathways involving mTOR and AMPK both of which regulate cellular energy status and respond to metabolic signals positioning ATG4C as a vital component in these pathways.

Alterations in ATG4C function have been linked to cancer and neurodegenerative disorders. In cancer dysregulated autophagy affects tumor growth and therapy resistance. ATG4C is related to Beclin 1 which regulates autophagy initiation in tumors. In neurodegeneration impaired autophagy exacerbates the accumulation of protein aggregates. Misfunction of ATG4C can influence these processes showing a direct connection to p62/SQSTM1 a protein involved in defective degradation that leads to neurodegenerative pathology.