Autophagy lysosome (Autophagy)

Autophagy is a pathway for intracellular degradation. It is a process of transporting damaged, denatured or senescent proteins and organelles into lysosomes for digestion and degradation. In biological evolution, autophagy is a conserved process, from yeast to plant cells to mammals, and many of these regulators find their homologs in multiple species. Somatic autophagy includes three ways, namely macroautophagy, microautophagy, and chaperone-mediated autophagy. Giant autophagy refers to the formation of vesicles in the cytoplasm. The process of transport to lysosomes for the degradation of aging or damaged organelles and proteins in cells. Microautophagy refers to the process by which lysosomes directly endocytose and degrade cellular material. Molecular chaperone-mediated cells Autophagy refers to the process by which soluble proteins in cells pass through a molecular chaperone and enter the lysosome to be degraded. Under normal physiological conditions, autophagy facilitates the cell to maintain its homeostasis; in the presence of stress, autophagy prevents the accumulation of toxic or carcinogenic damaged proteins and organelles, inhibiting cell carcinogenesis (Reggiori F, 2002; Shintani, T, 2004). ). The autophagy needs to go through the following four stages: Stage 1: Initiation of the phagophore After the cells receive autophagy and signal, they form a membrane structure somewhere in the cytoplasm and then expand. The structure was initially flat-sided, like an open pocket of lipid bilayers, which can be observed under electron microscopy and is called an autophagic membrane. This Moye is known as the isolation membrane, which is one of the signs of self-love. Stage 2: Formation of autophagosomes. The autophagic membrane is constantly "elongation", and the parts of the cytoplasm that need to be degraded, including the organelles, are all taken into the "pocket" and then "closure" into a closed spherical autophagosome. This autophagosome is like a large "liposome". Autophagosomes can be observed under electron microscopy and are the second marker of autophagy. Self-love has two characteristics, one is a two-layer membrane, and the twenty contains cytoplasmic components, such as mitochondria and endoplasmic reticulum fragments. Stage 3: Transportation and fusion of autophagosomes. At this stage, the formed autophagosomes can be fused to the endocytic phagocytosis, swallowing run, and endosome to form a lysosomal and inclusion fused veshisome. But these conditions are not necessary in the autophagy process. Stage 4: Degradation of autophagosomes. Autophagosomes fuse with lysosomes to form autolysosomes, during which the inner membrane of autophagosomes is degraded by lysosomal enzymes, and the contents of the two are integrated. The contents of the autophagosome are also degraded to obtain raw materials such as amino acids and fatty acids, which are transported to the cytoplasm for reuse by the cells, and the residues that cannot be recycled may be excreted or retained in the cytosol. (Gozuacik D, 2004). TOR itself is a serine/threonine kinase that regulates cell cycle, growth and proliferation. Under normal circumstances, TOR achieves control of autophagy by inhibiting the activity of the autophagy initiation molecule Atg1. In mammals, the homolog of TOR, mTOR, is in an activated state, and phosphorylation inhibits the function of the autophagy initiation molecule ULK1 and inhibits the occurrence of autophagy. TOR/mTOR can form two complexes of TORC1/mTORC1 and TORC2/mTORC2. mTORC1 includes mTOR, mLST8, PRAS40 and Raptor. . Raptor is a component sensitive to Rapamycin drugs, so Rapamycin is often used in autophagy studies to induce autophagy by specifically inhibiting the activity of mTORC1. In addition, mTORC1 regulates cell growth and proliferation through 4E-BP1 and S6K1 regulation of protein synthesis and ribosome biogenesis. mTORC2 includes mTOR, mSin1 and Rictor is not sensitive to Rapamycin. mTORC2 is involved in the regulation of cytoskeletal formation by phosphorylating Akt (protein kinase B) and PKC (protein kinase C), signaling to the small GTPases Rac1 and RhoA. AMPK is a protein kinase that regulates the metabolism of energy states in cells and plays an important role in the regulation of autophagy. At low ATP levels (such as starvation or hypoxia), AMPK can activate the level of AMP to activate, and phosphorylation aggravates the inhibition of Rheb by TSC1/2, which ultimately inhibits mTOR activity and induces autophagy. In addition, studies have shown that AMPK can directly phosphorylate Raptor and inhibit its activity, resulting in decreased activity of mTORC1. TSC1/2 can also integrate signals from PI3K-AKT and Raf-1-MEK1/2-ERK1/2 into mTORC1. When stimulated by a signal such as growth factor, Akt is activated to phosphorylate TSC2 and inhibit its binding to TSC1. Raf-1-MEK1/2-ERK1/2 also inhibits TSC1/TSC2 and ultimately activates Rheb-mTORC1. Inhibition of autophagy occurs (Meijer AJ, 2004; Liang XH, 1999; Paglin S, 2001).