Sestrin-like protein from Dictyostelium discoideum is involved in autophagy under starvation stress

Sestrins are highly conserved; stress inducible proteins that help maintain metabolic homeostasis and protect cells under stress conditions. They are up-regulated during stress and influence AMPK and mTOR pathways. Our objective was to find the role of Sestrin protein from Dictyostelium discoideum (Dd), a lower eukaryote where starvation stress initiates multicellular development. The single DdSesn-like gene was expressed and its endogenous functions were characterized. Both, the knockout and constitutively expressing strains were made and their involvement in starvation-induced autophagy was analyzed. Autophagic fluxes and ROS levels were also monitored. Additionally, overexpression of DdSesn decreased cell growth and showed a longer lag phase. Upon starvation both DdSesn and ROS levels increased. Sesn^OE showed reduced ROS levels while sesn^- showed increased ROS levels when compared to the wild type. Therefore, we suggest that increased sesn expression may be beneficial in reducing ROS levels during starvation. Deletion of sesn showed reduced autophagic flux and increased p4EBP1 levels. We show that DdSesn promotes autophagy in D. discoideum upon starvation.