Macroautophagosome

A macroautophagosome, commonly referred to simply as autophagosome, is a double-membrane vesicle involved in the process of macroautophagy, a cellular degradation pathway. This process is essential for the maintenance of cellular homeostasis by degrading and recycling cytoplasmic components, including damaged organelles, misfolded proteins, and pathogens.

The formation of a macroautophagosome begins with the nucleation of a phagophore, a small isolation membrane that expands and engulfs targeted cellular material. This membrane then elongates and closes upon itself to form a double-membrane vesicle. The macroautophagosome is characterized by its double membrane structure and typically ranges from 500 to 1500 nanometers in diameter.

Once formed, the macroautophagosome fuses with a lysosome to form an autolysosome, where the enclosed material is degraded by lysosomal enzymes. The resulting breakdown products are then released back into the cytoplasm for reuse in cellular metabolism.

The biogenesis of macroautophagosomes involves numerous autophagy-related (ATG) proteins, including the Atg5–Atg12 conjugation system and LC3 (microtubule-associated protein 1A/1B-light chain 3), which is lipidated to LC3-II and associates with the autophagosomal membrane, serving as a key marker for autophagosome formation.

Macroautophagosomes play a vital role in cellular adaptation to stress conditions, such as nutrient deprivation, and are implicated in various diseases, including neurodegeneration, cancer, and infections. Understanding their formation and function is crucial for exploring therapeutic strategies targeting autophagy-related pathways.