Autophagy degradation machinery

The autophagy degradation machinery is a highly conserved catabolic process responsible for the degradation and recycling of cytoplasmic components, including damaged organelles and misfolded proteins, via the lysosomal pathway [Mizushima et al., 2011, Cell]. This machinery is orchestrated by a series of autophagy-related (ATG) proteins that facilitate the formation of double-membrane vesicles called autophagosomes, which subsequently fuse with lysosomes for cargo digestion [Dikic & Elazar, 2018, Nat Rev Mol Cell Biol]. It serves as a critical quality control mechanism, maintaining cellular homeostasis under basal conditions and providing energy during nutrient deprivation [Levine & Kroemer, 2019, Cell]. Dysregulation of this machinery is implicated in a wide range of pathologies, including neurodegenerative diseases where protein aggregates accumulate, and cancer, where it plays a dual role as both a tumor suppressor and a survival mechanism for established tumors [Galluzzi et al., 2017, Nat Rev Drug Discov]. Therapeutic strategies involve either inducing autophagy to clear toxic aggregates or inhibiting it to sensitize cancer cells to chemotherapy [Klionsky et al., 2021, Autophagy].

Other names

MacroautophagyAutophagic pathwayLysosomal degradation pathwayATG-dependent degradation

Modulation of the autophagy pathway through mTOR inhibition (induction), PI3K inhibition (blockade of initiation), or lysosomal acidification blockade (blockade of degradation).