Sirt3 is critical for p53-mediated ferroptosis upon ROS-induced stress
作者机构：Department of GastroenterologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China Institute for Cancer Geneticsand Department of Pathology and Cell Biologyand Herbert Irving Comprehensive Cancer CenterCollege of Physicians&SurgeonsColumbia UniversityNew YorkNY 10032USA Department of GastroenterologySuzhou Ninth People’s HospitalSuzhou 215200China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2021年第13卷第2期
页 面：151-154页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
主 题：metabolism Lipid stress
摘 要：Dear Editor,p53 acts as a transcription factor to modulate various types of cellular processes to suppress tumor development(Tackmann and Zhang,2017).The exquisite regulation of p53 functions is of vital importance for cell fate *** it is well accepted that p53-mediated cell-cycle arrest,senescence,and apoptosis serve as major tumor suppression mechanisms,recent studies suggest that other unconventional activities such as ferroptosis are also critically involved in its tumor suppressor function(Li et al.,2012).We and others found that p53 plays an important role in modulating ferroptotic responses through its metabolic targets(Jiang et al.,2015;Jennis et al.,2016;Wang et al.,2016).Ferroptosis is a regulated form of iron-dependent,non-apoptotic cell death characterized by excessive reactive oxygen species(ROS)generation and accumulation of lipid peroxidates(Stockwell et al.,2020).Lipid peroxides are normally eliminated by glutathione peroxidase 4(GPX4)and its co-factor glutathione(GSH),which convert lipid hydroperoxides to non-toxic lipid ***,ferroptosis can be artificially induced by pharmacological agents that disrupt this lipid repair system,allowing lethal accumulation of lipid *** agents include direct GPX4 enzymatic inhibitors,as well as the small molecule erastin,which suppress glutathione synthesis and indirectly suppress GPX4 activation(Stockwell et al.,2020).Although activation of p53 expression is able to modulate ferroptosis induced by GPX4 inhibition in certain cell types(Jiang et al.,2015),p53-mediated ferroptotic responses are also observed upon ROS-induced stress,apparently through a GPX4-independent manner(Chu et al.,2019).Nevertheless,the molecular factors that modulate p53-dependent ferroptosis upon ROS stress need further ***3 is a NAD-dependent deacetylase predominantly localized in mitochondria,which functions in multiple metabolic pathways,including electron transport chain,fatty acid oxidation,a
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