Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing num...Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin I-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.展开更多
During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and...During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and regulatory mechanisms. Autophagy is defined as an autolytic process to clear damaged cellular organelles and recycle the nutrients via lysosomic degradation. The process of autophagy responds to special conditions such as nutrient withdrawal. Once autophagy is induced,phagophores form and then elongate and curve to form autophagosomes. Autophagosomes then engulf cargo,fuse with endosomes, and finally fuse with lysosomes for maturation. During the initiation process, the ATG1/ULK1(unc-51-like kinase 1) and VPS34(which encodes a class III phosphatidylinositol(Ptd Ins) 3-kinase) complexes are critical in recruitment and assembly of other complexes required for autophagy. The process of autophagy is regulated by autophagy related genes(ATGs). Amino acid and energy starvation mediate autophagy by activating m TORC1(mammalian target of rapamycin) and AMPactivated protein kinase(AMPK). AMPK is the energy status sensor, the core nutrient signaling component and the metabolic kinase of cells. This review mainly focuses on the mechanism of autophagy regulated by nutrient signaling especially for the two important complexes,ULK1 and VPS34.展开更多
文摘Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin I-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.
基金financial support from the China Scholarship Council, the National Basic Research Program of China (2013CB117301)the National Natural Science Foundation of China (31272448, 31472101, 31420103908, and 31528018)+3 种基金the 111 Project (B16044)Beijing Nova Program (xx2013055)Education Foundation of China Agricultural University "Dabeinong Education Fund" (1041-2415001)National Department Public Benefit Research Foundation (201403047) are gratefully acknowledged
文摘During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and regulatory mechanisms. Autophagy is defined as an autolytic process to clear damaged cellular organelles and recycle the nutrients via lysosomic degradation. The process of autophagy responds to special conditions such as nutrient withdrawal. Once autophagy is induced,phagophores form and then elongate and curve to form autophagosomes. Autophagosomes then engulf cargo,fuse with endosomes, and finally fuse with lysosomes for maturation. During the initiation process, the ATG1/ULK1(unc-51-like kinase 1) and VPS34(which encodes a class III phosphatidylinositol(Ptd Ins) 3-kinase) complexes are critical in recruitment and assembly of other complexes required for autophagy. The process of autophagy is regulated by autophagy related genes(ATGs). Amino acid and energy starvation mediate autophagy by activating m TORC1(mammalian target of rapamycin) and AMPactivated protein kinase(AMPK). AMPK is the energy status sensor, the core nutrient signaling component and the metabolic kinase of cells. This review mainly focuses on the mechanism of autophagy regulated by nutrient signaling especially for the two important complexes,ULK1 and VPS34.
