autophagosomal

Autophagosomal is an adjective relating to autophagosomes, the double‑membrane vesicles that sequester cytoplasmic material for degradation in autophagy. Autophagosomes are formed during cellular stress or nutrient deprivation and deliver their cargo to lysosomes for breakdown and recycling of macromolecules.

The formation of autophagosomal structures begins with initiation of autophagy. Under conditions such as nutrient scarcity, the ULK1 kinase complex is activated and promotes nucleation of the phagophore through the class III PI3K complex, which includes Beclin-1. As the isolation membrane expands, a set of autophagy-related (ATG) proteins drives elongation and closure. A central step is the lipidation of LC3 (ATG8 in yeast) to generate LC3-II, which decorates the autophagosomal membrane and is used as a marker of autophagosome formation.

Maturation involves the closure of the phagophore to form a complete autophagosome, followed by transport along microtubules to lysosomes. Fusion with lysosomes creates an autolysosome, where acidic hydrolases degrade the enclosed material. The resulting macromolecular components are recycled for cellular use. Selective forms of autophagy use cargo receptors, such as p62/SQSTM1, to recognize specific substrates and target them to autophagosomes.

Regulation of autophagosomal activity is tight and context dependent. Mechanisms include inhibition by mTORC1 under nutrient-rich conditions and activation by AMPK during energy stress. Disruptions in autophagosomal processes or dysfunction of autophagy genes can contribute to disease, including neurodegenerative disorders, cancer, and infections, highlighting the importance of proper autophagosomal function in cellular homeostasis.