Serum apolipoprotein H determines ferroptosis resistance by modulating cellular lipid composition.

IF 8.1 1区生物学 Q1 CELL BIOLOGY

Cell Death & Disease Pub Date : 2024-10-01 DOI:10.1038/s41419-024-07099-2

Xiang He, Jiahui Zhang, Masha Huang, Jie Wang, Simin Yang, Xiang Yu, Yingjie Xu, Wen Yang

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Abstract

Ferroptosis is a regulated cell death process dependent on iron, triggered by the accumulation of lipid peroxidation. The environmental context significantly impacts cellular sensitivities to ferroptosis. Serum, constituting the extracellular fluid composition in vivo, provides crucial environmental biomolecules. In this study, we investigated the influence of sera on ferroptosis induction, pinpointing the serum protein apolipoprotein H (APOH) as a pivotal inhibitor of ferroptosis. Moreover, we elucidated that APOH suppresses ferroptosis by activating the phosphoinositide 3-kinase (PI3K)-AKT-sterol regulatory element-binding proteins (SREBPs) pathway, thereby elevating stearoyl-CoA desaturase (SCD) levels and augmenting cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs). Furthermore, ApoHinfer, the peptide derivative of the active region of APOH, mimics its ferroptosis inhibitory activity. Our findings underscore the critical role of serum protein APOH in the inhibition of ferroptosis and indicates potential therapeutic applications in treating cancer and diseases associated with ferroptosis.

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血清载脂蛋白 H 通过调节细胞脂质组成决定铁变态反应抵抗力

铁中毒是一种依赖于铁的调节性细胞死亡过程，由脂质过氧化物的积累引发。环境背景对细胞对铁变态反应的敏感性有重大影响。构成体内细胞外液成分的血清提供了重要的环境生物大分子。在这项研究中，我们研究了血清对铁氧化诱导的影响，发现血清蛋白脂蛋白 H（APOH）是铁氧化的关键抑制剂。此外，我们还阐明了载脂蛋白H通过激活磷酸肌醇3-激酶（PI3K）-AKT-甾醇调节元件结合蛋白（SREBPs）通路，从而提高硬脂酰-CoA去饱和酶（SCD）的水平并增加细胞中含单不饱和脂肪酸的磷脂（MUFA-PLs）来抑制铁变态反应。此外，ApoHinfer 是 APOH 活性区的多肽衍生物，可模拟其铁蛋白沉积抑制活性。我们的研究结果强调了血清蛋白APOH在抑制铁嗜酸性蛋白形成中的关键作用，并指出了其在治疗癌症和与铁嗜酸性蛋白形成有关的疾病方面的潜在治疗应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death & Disease CELL BIOLOGY-

CiteScore

15.10

自引率

2.20%

发文量

935

审稿时长

2 months

期刊介绍： Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism