Friday, December 11, 2020

Autophagy is a process involving genes and enzymes related to autophagy

There are three known processes and pathways of autophagy


(1) Giant cell autophagy is the main way. Around the destroyed organelles, proteins and lipids form a meniscus-shaped double membrane, which then surrounds the vesicle-like autophagosome, which separates from the rest of the cytoplasmic components. The process requires LC3 protein similar to ubiquitin to bind to the lipid phosphatidylethanolamine (PE) on the surface of the autophagosome. This lipidated LC3-PE complex helps to close the autophagosome. Autophagosomes carry cleaned damaged organelles or unused proteins, pass through the cytoplasm, and fuse with lysosomes to form autophagolysosomes. This process requires the participation of various proteins including SNAREs and UVRAG; autophagosomes The content of the lysosome is degraded by the hydrolase provided in the lysosome, and then the degraded small molecular substances such as amino acids are released from the vesicles through the action of the permease and can be recycled and reused.


(2) Microcellular autophagy is a cytoplasmic substance that is directly swallowed into the lysosomal membrane or endocytic membrane body through the folding and indentation or cell protrusion, and then degraded by lysosomal proteases.


(3) Cellular autophagy (CMA) mediated by accessory proteins or molecular chaperones is complex and different from autophagy in giant and tiny cells. CMA is a specific pathway generated by the complex assembled by heat shock protein 70 (hsc70); this pathway selectively recognizes and helps cells containing individual protein substances similar to the KFERQ pentapeptide motif to pass through the lysosome barrier. Through the identification of hsc70, it binds to form a CMA-chaperone complex, unfolds the protein conformation, and moves to the lysosomal membrane-bound protein. With the help of the lysosomal hsc70 chaperone, it depends on the LAMP2A protein. , Translocation across the lysosome membrane to the lysosome, and then decomposed by the protease in the lysosomal lumen.


Autophagy is performed by the autophagy-related gene Atg. A simplified description of its activation mechanism can be regulated by regulating the activity of protein kinase mTOR and AMPK. It is induced by a complex of activated ULK and proteins including Beclin-1. Autophagy participates in the formation of autophagosomes and starts to activate the downstream autophagy components as described above.

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