Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Department of Life Sciences, Korea University, Seoul, Republic of Korea.
Trends Cell Biol. 2023 Dec;33(12):1088-1103. doi: 10.1016/j.tcb.2023.07.003. Epub 2023 Aug 7.
Ferroptosis is the type of cell death arising from uncontrolled and excessive lipid peroxidation. NADPH is essential for ferroptosis regulation because it supplies reducing equivalents for antioxidant defense systems and contributes to the generation of reactive oxygen species. Moreover, NADPH level serves as a biomarker for predicting the sensitivity of cells to ferroptosis. The ubiquitin-proteasome system governs the stability of many ferroptosis effectors. Recent research has revealed MARCHF6, the endoplasmic reticulum ubiquitin ligase, as an unprecedented NADPH sensor in the ubiquitin system and a critical regulator of ferroptosis involved in tumorigenesis and fetal development. This review summarizes the current understanding of NADPH metabolism and the ubiquitin-proteasome system in regulating ferroptosis and highlights the emerging importance of MARCHF6 as a vital connector between NADPH metabolism and ferroptosis.
铁死亡是一种由不受控制的过度脂质过氧化引起的细胞死亡类型。NADPH 对于铁死亡的调节至关重要，因为它为抗氧化防御系统提供还原当量，并有助于产生活性氧。此外，NADPH 水平可作为预测细胞对铁死亡敏感性的生物标志物。泛素-蛋白酶体系统控制着许多铁死亡效应物的稳定性。最近的研究揭示了内质网泛素连接酶 MARCHF6 作为泛素系统中一个前所未有的 NADPH 传感器，以及一个涉及肿瘤发生和胎儿发育的铁死亡的关键调节剂。本综述总结了 NADPH 代谢和泛素-蛋白酶体系统在调节铁死亡方面的最新认识，并强调了 MARCHF6 作为 NADPH 代谢和铁死亡之间重要连接物的新兴重要性。
