autofagosomas

Autophagosomes are double-membrane vesicles that sequester cytoplasmic material during macroautophagy. They originate from expanding phagophores and enclose cytosolic components, damaged organelles, or large protein aggregates, forming a sealed vesicle. After completion, autophagosomes fuse with lysosomes to create autolysosomes, where their contents are degraded and the resulting macromolecules are reused by the cell.

Biogenesis and structure of autophagosomes involve a highly regulated set of proteins. Initiation is driven by the ULK1 complex, activated when nutrient signaling inhibits mTOR. The class III PI3K complex Beclin1-PI3KC3 generates PI3P to recruit downstream factors that nucleate membranes. Expansion and closure rely on Atg conjugation systems, including Atg5-Atg12-Atg16L1 and the conversion of LC3 to LC3-II, which becomes associated with the autophagosomal membrane and serves as a marker for the mature vesicle. The resulting autophagosome is a distinct, double-membrane structure ready to engage lysosomes.

Selective autophagy involves cargo receptors such as p62/SQSTM1, NDP52 and optineurin that recognize ubiquitinated substrates and bind LC3 via LC3-interacting regions, thereby targeting specific cargo like damaged mitochondria (mitophagy) or protein aggregates (aggrephagy). Fusion with lysosomes requires Rab7 and SNARE proteins, including syntaxin-17, leading to the formation of autolysosomes where degradation occurs.

Function and significance of autophagosomes include maintaining cellular homeostasis during starvation, clearing damaged organelles, and regulating immune responses. Dysregulation of autophagosome formation or function has been linked to neurodegenerative diseases, infections, and cancer. Autophagosomes can be detected by LC3-II presence and, in ultrastructure studies, by characteristic double-membrane vesicles.