Autophagy is the regulated, self-degradative physiological process in the body that deals with destruction of cells in the body. The word autophagy is derived from Greek words “auto” meaning self and “phagy” meaning eating.

 

Autophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily conserved among eukaryotes and exquisitely regulated. This progress initiates with production of the autophagosome, a double-membrane intracellular structure of reticular origin that engulfs cytoplasmic contents and ultimately fuses with lysosomes for cargo degradation. Autophagy is induced by conditions of nutrient deprivation as well as physiological and pathological processes such as development, differentiation, neurodegenerative diseases, stress, infection, obesity, and cancer. Constitutive level of autophagy plays an important role in cellular homeostasis and maintains quality control of essential cellular components.[1]

自噬细胞动图

 

Autophagy pathway

 

There are three major forms of autophagycommonly described: Macroautophagy, Microautophagy, and mitophagy, along with chaperone-mediated autophagy (CMA).


• Macroautophagy is the primary pathway and initiates isolation of cytoplasmic targets via a double-membraned vesicle - the autophagosome.The autophagosome then travels through the cytoplasm of the cell to a lysosome, and the two organelles fuse. Within the newbuilt autolysosome, the contents of the autophagosome are degraded via acidic lysosomal hydrolases.


• Microautophagy, involves the direct engulfment of cytoplasmic material and organelles, such as the peroxisome and the nucleus into the lysosome. This occurs by invagination, meaning the inward folding of the lysosomal membrane, or cellular protrusion.


• Mitophagy is the selective degradation of mitochondria by autophagy. It is triggered by defective mitochondria following damage or oxidative stress. Mitophagy prevents cellular degeneration caused by accumulation of dysfunctional mitochondria. NIX and its regulator BNIP3 mediate mitophagy in mammals as well as PINK1 and parkin proteins. The occurrence of mitophagy is not limited to the damaged mitochondria but also involves undamaged ones.


• Chaperone-mediated autophagy (CMA) differs from the other autophagic pathways as it does not involve vesicle formation but, rather, a direct translocation of a specific set of proteins across the lysosomal membrane. The cytosolic chaperone hsc70, plays a major role in target recognition and transport to the lysosom. Targeted proteins must have an amino acid sequence a with pentapeptide motif biochemically related to KFERQ in order to be bound by hsc70.


• Other types of autophagy
     • piecemeal microautophagy of the nucleus
     • cytoplasm-to-vacuole targeting (Cvt) pathway

 

Related genes of knockout cell lines
AKT1 ATG14 ATG16L1 ATG3 ATG7 ATG8
BAD CAMKK2 DDIT4 EIF2AK3 HIF1A FRAP
IGF1R KRAS LAMP2 MAP2K1 MAP2K2 MAP3K7
MAPK1 MLST8 MTMR4 NRAS PIK3R2 PKA
RAF1 RPS6KB1 RRAS2 STK11 VAMP8