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Scientists discover a new phosphorylation at BECN1 for energy-sensing signaling on autophagy

Macroautophagy, referred to as autophagy, is an evolutionarily conserved catabolic process against a variety of cellular stresses, such as organelle damage, nutrient starvation, infection and protein aggregates. Autophagy involves sequester “cargo” of double-membrane-enclosed autophagosome and delivers cytoplasmic material to lysosome for degradation and recycle. More than 32 autophagy related proteins have been identified in yeast and various mammalian species. These Atgs are involved in the autophagy initiation, nucleation, elongation and fusion with lysosome. In all steps, autophagy can be well controlled by different molecules.

Recently, a research group led by Dr. Liu Zhixue from the Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences found that AMP-activated protein kinase (AMPK) regulates autophagy by phosphorylating BECN1 at Thr388. Phosphorylation of BECN1 is required for autophagy initiation upon glucose starvation. BECN1 T388A, a phosphorylation defective mutant, suppresses autophagy through decreasing the affinity between VPS34, ATG14L. BECN1 T388A mutant has a higher interaction to BCL2 than its wild-type counterpart. This mutant is easier to construct a dimmer. On the other hand, BECN1 phosphorylation mimic mutant, T388D, has a stronger binding to VPS34, ATG14L and promotes higher autophagy level than the wild-type control. These findings suggest a novel mechanism of autophagy regulation.

This work was published online in the AUTOPHAGY on June 15, 2016, as a research article entitled “AMPK regulates autophagy by phosphorylating BECN1 at Threonine 388”. This study was funded by research grants from National Natural Science Foundation of China, Ministry of Science and Technology of China.

Author Contact:
Liu Zhixue, Ph.D., Principal Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Tel: 86-21-54920976;
Fedex code: 281763261
E-mail: zxliu@sibs.ac.cn

AMPK regulates Autophagy process by directly phosphorylate Beclin1 on T388 site.
Image by Dr. Liu’s lab

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