Sestrin2-AMPK activation protects mitochondrial function against glucose deprivation-induced cytotoxicity

Cellular Signalling
Kyuhwa SeoSang Mi Shin

Abstract

Sestrin2 (SESN2) regulates redox-homeostasis and apoptosis in response to various stresses. Although the antioxidant effects of SESN2 have been well established, the roles of SESN2 in mitochondrial function and metabolic stress have not yet been elucidated. In this study, we investigated the role of SESN2 in mitochondrial dysfunction under glucose deprivation and related signaling mechanisms. Glucose deprivation significantly upregulated SESN2 expression in hepatocyte-derived cells. Antioxidant treatments repressed SESN2 induction under glucose deprivation, this result suggested that reactive oxygen species (ROS) production was involved in SESN2 induction. Moreover, NF-E2-related factor-2 (Nrf2) phosphorylation was accompanied in induction of SESN2 by glucose deprivation. To elucidate the functional role of SESN2, we examined cells that stably overexpressed SESN2. Overexpression of SESN2 inhibited glucose deprivation-induced ROS production and cell death. In addition, under glucose deprivation, the changes in mitochondrial membrane potential, ADP/ATP ratio, and mitochondrial DNA content were significantly restored in SESN2-overexpressing cells. Moreover, siRNA knockdown of SESN2 failed to prevent mitochondrial permeability tran...Continue Reading

References

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Citations

Jun 30, 2015·Journal of Neurogenetics·Yu-Ju Liu, Yijuang Chern
Mar 17, 2016·Radiation and Environmental Biophysics·Yue-Can ZengRong Wu
Mar 27, 2016·Apoptosis : an International Journal on Programmed Cell Death·Kyung Hwan JegalSang Chan Kim
May 7, 2016·Biological & Pharmaceutical Bulletin·Kyuhwa SeoSang Mi Shin
Nov 3, 2016·Biological & Pharmaceutical Bulletin·Suho SeoSang Mi Shin
Jul 7, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Xudan ShiJohn H Zhang
Jun 9, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nanhu QuanJi Li
May 7, 2020·Experimental and Therapeutic Medicine·Seunghyeong LeeKeun-Gyu Park
Sep 6, 2020·Molecular Biology Reports·Ashish KumarChandrima Shaha
Dec 24, 2019·Frontiers in Immunology·Li-Xue WangYong-Ming Yao
Dec 31, 2020·Human & Experimental Toxicology·Xiaobin LiuJinning Song
Dec 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jie Wang BJunlian Gu
Dec 15, 2020·Free Radical Biology & Medicine·Yunxia LiuNanhu Quan
May 12, 2020·Mechanisms of Ageing and Development·Xiaolan FanMingyao Yang
Feb 18, 2017·Chemico-biological Interactions·Seung Jung KimSung Hwan Ki

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