Lautofagosoma

Lautofagosoma, often referred to in Italian as l'autofagosoma, is a double-membrane vesicle that forms in eukaryotic cells during macroautophagy to sequester cytoplasmic material for degradation. It arises from an expanding isolation membrane, or phagophore, and grows to envelop portions of cytosol, organelles, and protein aggregates.

Formation and cargo selection involve a conserved set of autophagy-related proteins. Under nutrient stress, the ULK1 kinase complex initiates autophagy and activates a class III phosphatidylinositol 3-kinase (PI3K) complex that produces membrane nucleation sites. The membrane expands with Atg proteins and the conjugation of LC3 (to form LC3-II), which associates with the autophagosomal membrane and helps capture cargo. Cargo receptors such as p62/SQSTM1 link ubiquitinated substrates to LC3 for selective autophagy.

Functionally, the lautofagosoma serves to isolate and transport cytoplasmic material to the lysosome. It fuses with a lysosome to form an autolysosome, where lysosomal hydrolases degrade the enclosed contents. The resulting basic building blocks, such as amino acids and fatty acids, are recycled to support cellular metabolism and homeostasis.

Structure and regulation are tightly controlled. Autophagosomes are typically around 0.5 to 1 micrometer in diameter and possess two membranes. Their formation is negatively regulated by mTOR signaling and positively regulated by starvation- and stress-activated pathways, including ULK1 and Rab GTPases that mediate vesicle fusion.

Clinical and physiological relevance includes roles in development, neurodegeneration, cancer, and infection, reflecting the dual nature of autophagy as a cytoprotective and, in some contexts, cytotoxic process. See also autophagy, autophagosome, lysosome.