autophagosome maturation

Definition

Target type: biologicalprocess

Removal of PI3P and Atg8/LC3 after the closure of the phagophore and before the fusion with the endosome/lysosome (e.g. mammals and insects) or vacuole (yeast), and that very likely destabilizes other Atg proteins and thus enables their efficient dissociation and recycling. [GOC:autophagy, GOC:lf, PMID:28077293]

Autophagosome maturation is a complex process that involves the formation of a double-membrane vesicle called an autophagosome, which engulfs cellular components destined for degradation. This process is tightly regulated and involves multiple signaling pathways and protein interactions.

The initial step in autophagosome maturation is the formation of an isolation membrane, also known as a phagophore. This membrane originates from the endoplasmic reticulum (ER) and expands to enclose the cargo. The formation of the phagophore is mediated by a complex interplay of autophagy-related proteins (ATGs).

Once the phagophore has enclosed the cargo, it undergoes a series of elongation and closure steps to form a complete autophagosome. The elongation process involves the recruitment of additional membrane components and the assembly of specialized protein complexes. Key ATGs involved in this process include ATG5, ATG7, ATG12, and ATG16L1, which form a complex that facilitates the recruitment of the lipidated form of LC3 (LC3-II) to the phagophore membrane.

The closure of the autophagosome is a critical step that ensures the integrity of the double-membrane structure. This step involves the fusion of the two ends of the elongating phagophore, which is mediated by proteins such as ATG14L and ATG18.

Once the autophagosome is fully formed, it moves towards the lysosome, the cellular degradation center. The fusion of the autophagosome with the lysosome is mediated by the SNARE protein complex and involves the recruitment of lysosomal proteins like LAMP1 and LAMP2. This fusion event results in the formation of an autolysosome, where the engulfed cargo is degraded by lysosomal enzymes.

The degradation of the cargo within the autolysosome is a crucial aspect of autophagy. This process is facilitated by the acidic environment and the action of hydrolytic enzymes present in the lysosome. The breakdown products, such as amino acids, fatty acids, and sugars, can be recycled back into the cell to provide energy and building blocks.

Autophagosome maturation is a dynamic and tightly regulated process that is essential for cellular homeostasis and survival. Dysregulation of this process can lead to various diseases, including cancer, neurodegenerative disorders, and infectious diseases.'
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Proteins (4)

Compounds (31)