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The autophagic process is divided into five distinct stages: Initiation, phagophore nucleation, autophagosomal formation (elongation), autophagosome-lysosome fusion (autophagolysosome) and cargo degradation. [1] An autophagosome is a spherical structure with double layer membranes. [2]
Autophagy (or autophagocytosis; from the Greek αὐτόφαγος, autóphagos, meaning "self-devouring" [1] and κύτος, kýtos, meaning "hollow") [2] is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. [3]
Lysosome reformation: The vesicles released during phagolysosome resolution contribute to the reformation of lysosomes, thus supporting the next round of phagocytosis. Cargo degradation: The tubulation and vesicle release processes promote the complete degradation of phagolysosomal cargo.
This CMA-targeting motif is recognized by a cytosolic chaperone, heat shock cognate protein of 70 kDa (hsc70) which targets the substrate to the lysosome surface. [5] This substrate protein-chaperone complex binds to lysosome-associated membrane protein type 2A (LAMP-2A), which acts as the receptor for this pathway. [ 6 ]
This autophagic pathway engulfs multivesicular bodies formed after endocytosis therefore it plays role in membrane proteins turnover. [3] Microautophagy is also connected with organellar size maintenance, composition of biological membranes , cell survival under nitrogen restriction, and the transition pathway from starvation-induced growth ...
Intracellular digestion is divided into heterophagic digestion and autophagic digestion. [3] These two types take place in the lysosome and they both have very specific functions. [3] Heterophagic intracellular digestion has an important job which is to break down all molecules that are brought into a cell by endocytosis. [3]
Proteins that are degraded by chaperone-assisted selective autophagy include pathogenic forms of the Huntingtin protein, which cause Huntington's disease. [4] Furthermore, the expression of the cochaperone BAG3 is upregulated in aged neuronal cells, which correlates with an increased necessity to dispose oxidatively damaged proteins through autophagy. [3]
Figure from original paper, showing line diagrams of phagosomes arising from omegasomes (part D). The omegasome is a cell organelle consisting of lipid bilayer membranes enriched for phosphatidylinositol 3-phosphate (abbreviated PI(3)P or PtdIns3P), and related to a process of autophagy. [1]