The new mechanism of AMPK signaling regulating autophagy

Autophagy is a process of degrading cytoplasmic proteins and organelles relying on lysosomal pathway, and it has high conservatism in evolution. It exists widely in cells of animals from the yeast, nematodes, and fruit flies to higher vertebrates. In mammals, when cells sense external stimulation and nutritional signals, they would meet the physical needs of cells to promote the body's metabolism of certain proteins by degrading macromolecule like organelles which lose cell function and proteins which lose normal function. Autophagy not only provides recyclable materials for cell repair and cell regeneration but also can help cells resist pathogen invasion and nutritional deficiencies. Therefore, autophagy is generally considered as patron saint of sustaining cell life and maintenance its stability. However, the process of autophagy is extremely complicated, especially the fine regulation mechanism of autophagy. Explore how nutrition and hunger signals autophagy signals are integrated and transmitted to the downstream of autophagy has always been a hot topic of biological research. And all the studies can’t leave the use of different kinds of recombinant proteins such as recombinant horse proteins.

The formation of VPS34-VPS15-Beclin1 core complex would happen in the initial stage of autophagy. With other autophagy-related proteins such as Atg14L (autophagy-related protein 14) adding to the core complex, VPS34 (Ⅲ type phosphatidylinositol muscle alcohol 3-kinase) would gradually be activated and produce PtdIns3 P (phosphatidylinositol 3-phosphate) which plays an important promoting role on autophagic vacuole spreading taking PtdIns (phosphatidylinositol) as a substrate. When autophagy does not happen, Beclin1 would combine with Bcl2 and stay in resting state. Many kinases related to nutrition and growth such as mTOR and EGFR all can conduct phosphorylation on core scaffold protein Beclin1 in VPS34-VPS15-Beclin1 core complex to control the lipase activity of VPS34 in the way of changing the way the components of the complex, thereby affecting whether to conduct autophagy.

AMPK is an important kinase of cellular energy sensing and cell signaling regulation in autophagy process. Through research using recombinant rat proteins, researchers found that glucose would activate AMPK under condition of starvation, leading threonine 388 site in autophagic gene Beclin1 to show phosphorylation, promoting the dissociation of autophagy gene Beclin1 and Bcl2 and promoting the combination of Beclin1, VPS34 and Atg14L. These dissociation and binding changes makes VPS34 show extremely powerful catalytic activity, thereby producing a large number of PtdIns3 P to promote autophagic vacuoles to be generated at a near-hurricane-like velocity speed, greatly contributing to the occurrence and development of autophagy.

The study reveals the important role of Beclin1-T388 site in AMPK-mediated autophagy process during glucose deprivation, which provides important theoretical basis and feasible drug targets to further explore the molecular mechanism of autophagy and treatment of autophagy-related diseases and neurodegenerative diseases. Flarebio provides you with recombinant proteins like recombinant Cdh10 with good quality.