Dr. Guang-Chao Chen, an Associate Research Fellow at the Institute of Biological Chemistry in Academia Sinica used fruit fly (Drosophila) adult midgut and mammalian cells to investigate the role of autophagy (degradation of cell superfluous cell components) under oxidative stress (a possible cause of many human diseases). They showed that autophagy not only degrades damaged organelles and proteins but, more importantly, plays an important role in maintaining tissue homeostasis by regulating stem cell proliferation and cell death in response to oxidative stress. The study was published in the journal Developmental Cell on December 9, 2013, and was selected as the Editors’ Choice in Cell Biology in the December 17, 2013 issue of Science Signaling.

        Oxidation in cells causes damage to cellular organelles and proteins and is considered to be the cause of several human diseases. Oxidative stress is caused by excessive production of reactive oxygen species (ROS) which are chemically reactive molecules containing oxygen that are often termed “free radicals”. Oxidative stress activates “autophagy”, a cell self-protection mechanism through which a double membrane structure is formed to engulf and recycle damaged organelles and proteins, thus promoting cell survival. However, the regulatory mechanism and physiological function of autophagy under conditions of oxidative stress remains unclear.

        In this study, Dr. Chen and colleagues used fruit fly (Drosophila) adult midgut and mammalian cells as model systems. They discovered that the protein Atg9, an essential component of autophagy, directly interacts with Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2) to regulate ROS-induced c-Jun N-terminal kinase (JNK) activation and JNK-mediated downstream protective mechanisms, including autophagy (to repair damaged cells), stem cell proliferation (to replace dead cells), and cell death (to remove unrepaired cells). Moreover, they found that oxidative stress-induced autophagy can regulate JNK activity through a negative feedback mechanism to prevent the over activation of JNK-mediated stress responses, thereby helping the maintenance of tissue homeostasis. The research team also identified similar regulatory mechanisms in human cells. The findings of this study not only provide insights into the role of autophagy under oxidative stress conditions, but also suggest new directions for the development of therapeutic interventions for autophagy and oxidative stress-related diseases.

        The complete article entitled “Atg9 Interacts with dTRAF2/TRAF6 to Regulate Oxidative Stress-Induced JNK Activation and Autophagy Induction” can be found at the Developmental Cell journal website at:

http://www.cell.com/developmental-cell/abstract/S1534-5807(13)00634-5.  

        The complete list of authors is: Hong-Wen Tang, Hsiao-Man Liao, Wen-Hsin Peng, Hong-Ru Lin, Chun-Hong Chen, Guang-Chao Chen.