autophagosom

An autophagosom, also called an autophagosome, is a double-membrane vesicle that forms during macroautophagy to sequester cytoplasmic material for degradation. It originates from a phagophore that expands and closes, capturing cytosolic components such as damaged organelles, protein aggregates, and other cellular cargo. The process relies on autophagy-related (ATG) proteins, including the Atg5–Atg12–Atg16L1 complex and the lipidation of LC3 (ATG8) to phosphatidylethanolamine, which labels the growing membrane with LC3-II and helps recruit cargo and autophagy receptors.

Cargo selection can be selective or nonselective. Receptors such as p62/SQSTM1 and NBR1 bind ubiquitinated cargo and link it to LC3 on the autophagosomal membrane, promoting targeted sequestration of specific substrates like mitochondria (mitophagy), peroxisomes (pexophagy), or protein aggregates.

Maturation involves fusion of the autophagosome with a lysosome, aided by SNAREs, Rab GTPases, and related tethering factors, to form the autolysosome. Inside this degradative compartment, lysosomal hydrolases break down the cargo, and resulting macromolecules are recycled to the cytosol for reuse.

Autophagosomes play a central role in cellular homeostasis, especially under nutrient stress, by providing a controlled mechanism to recycle components and maintain energy balance. Dysfunction of autophagosome formation or clearance is associated with aging and various diseases, including neurodegenerative disorders, infections, and cancer. The process is tightly regulated by nutrient and energy sensing pathways, notably mTORC1 and AMPK, which influence the initiation of autophagosome formation.