Murat Artana, Jooyeon Sohnb, Cheolju Leec,*, Seung-Yeol Parkd,*, and Seung-Jae V. Leeb,*
aDepartment of Life Sciences, Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria; bDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea; cCenter for Theragnosis, Korea Institute of Science and Technology, Seoul, South Korea; dDepartment of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea
The Golgi apparatus regulates the process of modification and subcellular localization of macromolecules, including proteins and lipids. Aberrant protein sorting caused by defects in the Golgi leads to various diseases in mammals. However, the role of the Golgi apparatus in organismal longevity remained largely unknown. By employing a quantitative proteomic approach, we demonstrated that MON-2, an evolutionarily conserved Arf-GEF protein implicated in Golgi-to-endosome trafficking, promotes longevity via upregulating macroautophagy/autophagy in C. elegans. Our data using cultured mammalian cells indicate that MON2 translocates from the Golgi to the endosome under starvation conditions, subsequently increasing autophagic flux by binding LGG-1/GABARAPL2. Thus, Golgi-to-endosome trafficking appears to be an evolutionarily conserved process for the upregulation of autophagy, which contributes to organismal longevity.