autophagosomit

Autophagosomit (autophagosomes) are double-membrane–enclosed vesicles that sequester cytoplasmic material for degradation in lysosomes, primarily as part of macroautophagy. They form in response to cellular stress or nutrient limitation and serve to recycle damaged organelles, aggregated proteins, and other cytoplasmic constituents, contributing to cellular homeostasis and energy balance.

Biogenesis and composition: Autophagosome formation begins with the nucleation of a phagophore (isolation membrane) that expands and closes into a sealed vesicle. This process involves a set of Atg proteins and regulatory complexes, including the ULK1 kinase complex, the class III PI3-kinase complex generating PI3P, and the Atg5–Atg12–Atg16L1 complex. A key step is the lipidation of LC3 (the mammalian homolog of Atg8), producing LC3-II that associates with the autophagosomal membrane and marks its surface. Cargo receptors such as p62/SQSTM1 and NDP52 help recruit ubiquitinated substrates to the forming autophagosome by binding both LC3 and ubiquitin signals. Maturation requires closure of the membrane and subsequent fusion with lysosomes, aided by SNAREs and small GTPases.

Function and significance: Autophagosomit play a central role in cellular quality control, supporting adaptation to starvation, removal of damaged organelles (mitophagy, pexophagy, etc.), and innate immune responses through xenophagy. Dysregulation of autophagosome formation or clearance is linked to neurodegenerative diseases, infections, and cancer.

Detection and variation: Electron microscopy reveals the characteristic double-membrane vesicles; LC3-II and other autophagy markers are used in assays. Autophagosomit are part of a broader autophagy system that also includes microautophagy and chaperone-mediated autophagy, each with distinct mechanisms.