autofagosoma

Autofagosoma, also known as the autophagosome, is a double-membrane–bound vesicle that sequesters cytoplasmic material for degradation in lysosomes as part of macroautophagy. It plays a central role in cellular quality control, energy homeostasis, and response to stress by delivering damaged organelles, proteins, and pathogens to the lysosome for breakdown and recycling.

Structurally, autofagosomes are typically around 0.5 to 1 micrometer in diameter and bear a characteristic double membrane. The surface is decorated with autophagy-related (ATG) proteins, including LC3, which is processed to LC3-II and associates with the membrane. Cargo can be selected non-specifically or via receptors such as p62/SQSTM1, NBR1, or optineurin that recognize ubiquitinated cargo and link it to LC3 on the growing membrane.

Biogenesis begins with initiation by the ULK1 complex, activated when nutrient-sensing pathways relieve mTORC1 inhibition. The class III PI3-kinase complex (Vps34) generates PI3P to recruit effector proteins and nucleate a phagophore. Elongation and closure involve ATG conjugation systems: ATG12–ATG5–ATG16L1 and the conjugation of LC3 to phosphatidylethanolamine (PE), which helps expand and seal the membrane around the cargo to form the autofagosoma.

Fusion with lysosomes follows, mediated by SNAREs and tethering factors such as the HOPS complex and Rab7, producing an autolysosome where lysosomal hydrolases degrade the contents and recycle basic building blocks.

Regulation of autofagosome formation is controlled by nutrient and energy sensors, notably mTORC1 and AMPK. The process is central to selective autophagy as well, using cargo receptors to target specific substrates such as damaged mitochondria (mitophagy) or invading pathogens (xenophagy). Detection methods include electron microscopy, LC3 puncta assays, and p62 degradation studies. Clinical relevance spans neurodegeneration, infection, and cancer, where autophagy can be protective or contributory depending on context.