Autophagosomer

Autophagosomer, more commonly referred to as the autophagosome in current terminology, is a double-membrane vesicle that sequesters cytoplasmic material for degradation in lysosomes as part of the autophagy pathway. It is formed during cellular responses to nutrient limitation, stress, and developmental cues, helping to recycle macromolecules and clear damaged components.

Biogenesis begins with initiation of the phagophore by a nutrient-sensing signaling network. The ULK1 kinase complex activates downstream nucleation through the class III PI3K complex (Beclin-1-PI3KC3), generating membranes that expand and enwrap cytoplasmic cargo. Conjugation systems drive elongation: ATG5-ATG12-ATG16L1 acts as an E3-like ligase, and LC3/Atg8 is lipidated to form LC3-II, which decorates the growing autophagosomal membrane and facilitates cargo capture.

Cargo selection can be non-selective during starvation or selective via receptors such as p62/SQSTM1, NBR1, and OPTN that link ubiquitinated cargo to LC3 on the membrane. Once the cargo is enclosed, the autophagosome matures and fuses with a lysosome to form an autolysosome, where lysosomal hydrolases degrade the contents, releasing basic biomolecules for reuse.

Regulation primarily involves inhibition by mTORC1 under nutrient-rich conditions and activation by AMPK during energy stress. Autophagosomes are central to cellular homeostasis, stress responses, development, and immunity, with dysregulation linked to neurodegenerative diseases, cancer, and infections. In research, autophagosomes are often tracked by LC3-II puncta and cargo receptors as markers of autophagic flux.