Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells.
Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells.
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DOI：
10.1002/advs.202100997
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Luo Z
中科院分区：
文献类型：
--
作者：
Yao X;Li W;Fang D;Xiao C;Wu X;Li M;Luo Z
铁凋亡是一种新的调节性细胞死亡形式，其特征在于铁依赖性致死性脂质过氧化物的积累，并涉及许多危重疾病。近年来的研究表明，糖酵解、磷酸戊糖途径（PPP）和三羧酸循环等细胞能量代谢活动参与了还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）、谷胱甘肽（GSH）和活性氧（ROS）等关键性铁凋亡标志物的调节，从而在铁凋亡中发挥了潜在的调节作用。值得注意的是，肿瘤细胞可以激活适应性代谢反应，以抑制铁凋亡，从而进行自我保护，例如糖酵解和PPP的上调。由于肿瘤细胞的快速增殖和代谢速率的增强，肿瘤能量代谢已成为破坏氧化还原稳态和诱导铁凋亡的靶点。基于这些新的见解，这些肿瘤特异性代谢异常的调节影响被系统地表征，例如通过谷氨酰胺利用对铁凋亡的重新连接葡萄糖代谢和代谢补偿，并分析了潜在的分子机制。此外，这些基于铁凋亡的治疗策略也通过利用这些代谢脆弱性进行了讨论，这可能为临床肿瘤治疗开辟新的途径。铁凋亡受多种代谢途径的调节，但很少研究能量代谢的参与。这篇综述讨论了各种肿瘤代谢表型在肿瘤景观中对铁凋亡调控的功能作用，这可能会提高对肿瘤铁凋亡网络的理解，并为开发基于铁凋亡的新疗法提供启示。
Ferroptosis is a new form of regulated cell death, which is characterized by the iron‐dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self‐preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those‐tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis‐based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context. Ferroptosis is regulated by a variety of metabolic pathways, but the involvement of energy metabolism is rarely investigated. This review discusses the functional roles of various tumor metabolic phenotypes on ferroptosis regulation in the tumor landscape, which may improve the understanding of the tumor ferroptosis network and provide implications for the development of novel ferroptosis‐based therapies.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
影响因子：
29
作者：
Corbet, Cyril;Pinto, Adan;Feron, Olivier
通讯作者：
Feron, Olivier
影响因子：
21.1
作者：
Anderson NM;Mucka P;Kern JG;Feng H
通讯作者：
Feng H