Autophagy is a process involving the structure of the cell itself, through the lysosomal machinery, responsible for the transport of damaged organelles, misfolded proteins, and other macromolecules to lysosomes for degradation and reuse of evolutionally conserved processes. Autophagy is a phenomenon widely present in eukaryotic cells and can be divided into three categories: macroautophagy, microautophagy, and chaperone-mediated autophagy. This is a strictly regulated step, which is the routine step of cell growth, development, and homeostasis, and is helpful to maintain a balanced state of cellular products during synthesis, degradation, and subsequent cycles. Many studies have shown that autophagy is triggered in different degrees in the process of differentiation of many cells, such as participating in angiogenesis, osteogenic differentiation, adipogenesis, neurogenesis and so on.



The formation of autophagosomes


The occurrence of autophagic effects depends on the completion of the autophagy flux process, which means the complete dynamic process of autophagy, including the formation of autophagosomes, fusion of autophagosomes and lysosomes, and subsequent degradation and recycling.


Macroautophagy, microautophagy and chaperone-mediated autophagy are mediated by autophagy-related genes and their associated enzymes. Macroautophagy can be subdivided into bulk and selective autophagy. Selective autophagy is further subdivided into mitophagy, lipid autophagy, peroxisome autophagy, chloroplast autophagy and ribosome autophagy, etc.




Macroautophagy is the main autophagic pathway, which is mainly used to remove damaged organelles or unused proteins. First, phagocytes engulf substances to be degraded and form autophagosomes around damaged organelles. The autophagosome then travels through the cytoplasm of the cell to the lysosome, where the two organelles fuse. In the lysosome, the contents of the autophagosome are degraded by acid lysosomal hydrolases.




Microautophagy involves the direct phagocytosis of cytoplasmic substances into lysosomes. This occurs through invagination, meaning that the lysosomal membrane folds inward or the cell protrudes outward.



Comparison of macroautophagy and microautophagy


Chaperone-mediated Autophagy


Chaperone-mediated autophagy (CMA) is a very complex and specific pathway involving the recognition of hsc70-containing complexes. This means that the protein must contain a recognition site for the hsc70 complex, which will enable it to bind to this chaperone, forming a CMA-substrate/chaperone complex. This complex then moves to a lysosomal membrane-bound protein, which will recognize and bind to the CMA receptor. After recognition, the substrate protein is unfolded and passes through the lysosomal membrane with the help of the lysosomal hsc70 chaperone. CMA is significantly different from other types of autophagy. It transports protein substances one by one, and it is extremely selective for which substances cross the lysosomal barrier.




Mitophagy is the selective degradation of damaged or undamaged mitochondria through autophagy. Mitochondrial defects often occur after experiencing injury or stress. Mitochondrial phagocytosis promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria, which can lead to cellular degeneration. In mammals, it is mediatedby Atg3 in yeast, NIX and its regulator BNIP3. Mitochondrial phagocytosis is regulated by PINK1 and parkin proteins.




Lipoautophagy is the degradation of lipids through autophagy, and this function exists in both animal and fungal cells. However, the role of lipophagocytosis in plant cells remains elusive. In lipid phagocytosis, the targets are lipid structures called lipid droplets (LDs), with a predominantly triacylglycerol (TAGs) core, and spherical organelles composed of monolayers of phospholipids and membrane proteins. In animal cells, the major lipophagy pathway is the phagocytosis of LD by phagocytes, known as macroautophagy. On the other hand, in fungal cells, lipid metabolism is the main pathway, especially well-studied in budding yeast and Saccharomyces cerevisiae. Lipophagocytosis was first discovered in mice and published in 2009.

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