School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Microbiol Res. 2019 Mar;220:61-71. doi: 10.1016/j.micres.2018.12.006. Epub 2018 Dec 28.
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 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.
Sestrins 是高度保守的应激诱导蛋白，有助于维持代谢平衡并保护细胞在应激条件下。它们在应激时上调，并影响 AMPK 和 mTOR 途径。我们的目的是找到来自黏菌（Dictyostelium discoideum）的 Sestrin 蛋白的作用，黏菌是一种低等真核生物，饥饿应激会引发细胞的多细胞发育。我们表达了单一的 DdSesn 样基因，并对其内源性功能进行了表征。我们构建了敲除和组成型表达两种菌株，并分析了它们在饥饿诱导的自噬中的作用。还监测了自噬通量和 ROS 水平。此外，DdSesn 的过表达会降低细胞生长并表现出更长的迟滞期。在饥饿时，Sesn 和 ROS 水平都增加了。Sesn 显示出降低的 ROS 水平，而 sesn 显示出增加的 ROS 水平，与野生型相比。因此，我们认为在饥饿期间增加 sesn 的表达可能有助于降低 ROS 水平。Sesn 的缺失显示出降低的自噬通量和增加的 p4EBP1 水平。我们表明，DdSesn 在饥饿时促进黏菌的自噬。
