报告摘要：

Ferroptosis has emerged as a new form of regulated necrosis that is implicated in various human diseases. However, the precise molecular mechanisms and biological functions of ferroptosis remain poorly understood.  Our recently work show that the extracellular iron carrier protein transferrin and the intracellular metabolic process glutaminolysis are required for the execution of a form of programmed necrosis known as ferroptosis. Inhibition of ferroptosis can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases. To further understand the mechanisms of ferroptosis, we performed genome-wide RNAi screening and identified multiple autophagy-related genes as positive regulators of ferroptosis. Ferroptosis induction led to autophagy activation and consequent degradation of ferritin and ferritinophagy cargo receptor NCOA4. Consistently, inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroptotic cell death. Therefore, ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.

报告人简介： 施中东，安徽寿县人，天津大学本科和硕士，纽约城市大学生物医学工程博士，纽约纪念斯隆凯特琳癌症中心发育生物学博士后。博士期间利用3D培养技术研究血管内壁增生和肿瘤迁移的机械力学信号转导机理。博士后期间从事人诱导多能干细胞体细胞重编程、干细胞定向分化和基因组编辑技术的研究，建立了高效的干细胞基因组编辑技术－iCRISPR平台，并利用此平台进一步建立了研究人胰脏发育和糖尿病致病机理的基于干细胞和基因编辑的模型。目前的工作集中在研究和开发与衰老相关疾病的细胞疗法和基因疗法。在Cell Stem Cell, Cell Reports等杂志发表第一作者和通讯作者论文11篇，论文总引用超过1000次（Google Scholar）。此外还参与编写了4本专业图书。已被邀请和挑选做会议口头报告8次，包括ISSCR meeting, NYSTEM meeting, CFF conference等。目前担任20多个杂志的审稿人。