Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases,such as tumor suppression.Though initially being found from anticancer drug screening...Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases,such as tumor suppression.Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development,numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes,including several tumor suppressors and oncogenes.In this review,we introduce the basic concepts of ferroptosis,characterized by the features of non-apoptotic,iron-dependent,and overwhelmed accumulation of lipid peroxides,and the underlying regulated circuits are considered to be pro-ferroptotic pathways.Then,we discuss several established lipid peroxidation defending systems within cells,including SLC7A11/GPX4,FSP1/CoQ,GCH1/BH4,and mitochondria DHODH/CoQ,all of which serve as anti-ferroptotic pathways to prevent ferroptosis.Moreover,we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways.The regulation of proand anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a contextdependent manner,highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.展开更多
基金the funding support from National Natural Science Foundation of China(82103272 to Y.Zhang)Xi’an Jiaotong University(xtr042021011 to Y.Zhang)+1 种基金Department of Science and Technology of Shaanxi Province(2022KW-48 to J Chen)supported by Top Young Talents Programme at Xi’an Jiaotong University。
文摘Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases,such as tumor suppression.Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development,numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes,including several tumor suppressors and oncogenes.In this review,we introduce the basic concepts of ferroptosis,characterized by the features of non-apoptotic,iron-dependent,and overwhelmed accumulation of lipid peroxides,and the underlying regulated circuits are considered to be pro-ferroptotic pathways.Then,we discuss several established lipid peroxidation defending systems within cells,including SLC7A11/GPX4,FSP1/CoQ,GCH1/BH4,and mitochondria DHODH/CoQ,all of which serve as anti-ferroptotic pathways to prevent ferroptosis.Moreover,we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways.The regulation of proand anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a contextdependent manner,highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.
