A team led by Dr. Ruey-Hwa Chen, a Distinguished Research Fellow at the Institute of Biological Chemistry recently discovered that a KLHL20-based ubiquitin ligase controls the termination of autophagy. The research was published in the top molecular and cell biology journal Molecular Cell on December 10, 2015.
　　Autophagy is a cell self-eating process through which cellular components are delivered from the cell cytoplasm to cellular organelles called lysosomes for degradation and recycling. Autophagy is also important for removing harmful substances such as damaged organelles and infectious agents. Autophagy induction plays a key role in maintaining cell homeostasis in response to various stressed conditions. However, excessive autophagy leads to unrestrained cellular degradation, which can lead to detrimental effects. It remains unknown how the autophagy process is turned off once it is induced.
　　Dr. Chen’s research team found that a protein called KLHL20 plays a master role in autophagy termination. KLHL20 forms a ubiquitin ligase complex with Cul3. Upon autophagy induction, this complex participates in a feedback regulation to orchestrate the ubiquitination and degradation of multiple autophagy-initiating factors, such as ULK1, VPS34 and Beclin-1. Their degradation in turn promotes the degradation of other autophagy proteins, such as ATG13 and ATG14. These degradation events collectively lead to the termination of the autophagy process.
　　Another highlight of the study is the discovery of the physiological and pathological importance of autophagy termination. Using cell-based studies and mouse models, the team found that failure of autophagy termination promotes cell death and muscle atrophy, indicating a key role of autophagy termination in maintaining cell survival and tissue homeostasis.
　　The full article entitled “Cul3-KLHL20 ubiquitin ligase governs the turnover of ULK1 and VPS34 complexes to control autophagy termination” can be found online at the Molecular Cell website at: http://www.cell.com/molecular-cell/abstract/S1097-2765(15)00861-8
　　The full list of authors is: Chin-Chih Liu, Yu-Ching Lin, Yu-Hsuan Chen, Chun-Ming Chen, Liang-Yu Pang, Hsuan-An Chen, Pei-Rung Wu, Mei-Yao Lin, Si-Tse Jiang, Ting-Fen Tsai, and Ruey-Hwa Chen.