Autophagy pathway proteins (ATG proteins)

Autophagy pathway proteins, primarily the autophagy-related (ATG) proteins, constitute the core machinery responsible for macroautophagy, a highly conserved cellular degradation and recycling process. This pathway involves the sequestration of cytoplasmic components, such as damaged organelles, misfolded protein aggregates, and intracellular pathogens, into double-membrane vesicles called autophagosomes, which subsequently fuse with lysosomes for enzymatic degradation (Mizushima et al., 2011, Nature). Key proteins in this pathway include the ULK1 initiation complex, the Beclin-1/class III PI3K nucleation complex, and the ATG5-ATG12-ATG16L1 conjugation system, all of which are essential for maintaining cellular homeostasis and responding to nutrient deprivation or stress (Galluzzi et al., 2017, EMBO J). Dysregulation of these proteins is heavily implicated in various pathologies; for instance, impaired autophagy contributes to the accumulation of toxic aggregates in neurodegenerative diseases like Alzheimer's and Parkinson's, while in cancer, the pathway exhibits a complex dual role by suppressing early tumor initiation but promoting the survival of established tumors under metabolic stress (Levine & Kroemer, 2019, Cell). Pharmacological modulation of the autophagy pathway is a significant therapeutic strategy, with mTOR inhibitors like rapamycin serving as potent activators to enhance clearance of debris, and lysosomotropic agents like hydroxychloroquine serving as inhibitors to sensitize cancer cells to chemotherapy (Kundu & Thompson, 2008, Annu Rev Cell Dev Biol).

Other names

Autophagy-related proteinsMacroautophagy machineryATG family proteinsAutophagy core proteins

mTOR inhibition (autophagy induction); Lysosomal acidification inhibition (autophagy blockade); PI3K inhibition (early-stage autophagy inhibition); ULK1 inhibition