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Abstract：
We highlight the latest work of Qiu et al. on the core mechanism of ferroptosis induced by rare phospholipids with two polyunsaturated fatty acyl tails (PL-PUFA2s), which has been published in Cell. It has long been acknowledged that PLs containing one PUFA tail (PL-PUFA1s) serve as substrates for phospholipid peroxidation during the process of ferroptosis, owing to their susceptibility to oxidation and prevalence in vivo. However, the authors note that PL-PUFA2s, rather than PL-PUFA1s, represent critical lipid classes involved in the pro-ferroptosis process. Exogenous phosphatidylcholine-PUFA2s accumulate in mitochondria and combine with Complex I within the electron transport chain, thereby potentially resulting in an elevation of mitochondrial reactive oxygen species levels. Then, these mitochondrial peroxides prompt the substantial accumulation of peroxides within the endoplasmic reticulum, ultimately culminating in ferroptosis. These findings shed light on the potential molecular mechanisms underlying the induction of ferroptosis by dietary PL-PUFA2s and offer novel insights for both the evaluation of cellular iron death sensitivity and the treatment of cancer. This article will provide a more comprehensive elucidation of the paper and facilitate an enhanced understanding of the underlying mechanisms for readers.
摘要：
我们重点介绍邱等人的最新作品。关于具有两个多不饱和脂肪酰尾巴的稀有磷脂（PL-PUFA2s）诱导铁死亡的核心机制，已在Cell上发表。长期以来，人们一直认为含有一个PUFA尾部的PL（PL-PUFA1s）在铁凋亡过程中作为磷脂过氧化的底物，由于它们对体内氧化和流行的敏感性。然而,作者指出，PL-PUFA2s，而不是PL-PUFA1s，代表参与促铁蛋白过程的关键脂质类别。外源性磷脂酰胆碱-PUFA2s在线粒体中积累，并在电子传递链中与复合物I结合，从而可能导致线粒体活性氧水平的升高。然后，这些线粒体过氧化物促使内质网内的过氧化物大量积累，最终导致铁中毒。这些发现揭示了膳食PL-PUFA2诱导铁凋亡的潜在分子机制，并为评估细胞铁死亡敏感性和癌症治疗提供了新的见解。本文将对论文进行更全面的阐述，并促进读者对潜在机制的理解。
