Cellular quality control systems sense and mediate homeostatic responses to prevent the buildup of aberrant macromolecules, which arise from errors during biosynthesis, damage by environmental insults, or imbalances in enzymatic and metabolic activity. Lipids are structurally diverse macromolecules that have many important cellular functions, ranging from structural roles in membranes to functions as signaling and energy-storage molecules. As with other macromolecules, lipids can be damaged (e.g., oxidized), and cells require quality control systems to ensure that nonfunctional and potentially toxic lipids do not accumulate. Ferroptosis is a form of cell death that results from the failure of lipid quality control and the consequent accumulation of oxidatively damaged phospholipids. In this review, we describe a framework for lipid quality control, using ferroptosis as an illustrative example to highlight concepts related to lipid damage, membrane remodeling, and suppression or detoxification of lipid damage via preemptive and damage-repair lipid quality control pathways.Expected final online publication date for the Annual Review of Biochemistry , Volume 93 is June 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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脂质质量控制和铁死亡：从概念到机制

细胞质量控制系统感知并调节稳态反应，以防止异常大分子的积累，这些异常大分子是由于生物合成过程中的错误、环境损害或酶促和代谢活性失衡而引起的。脂质是结构多样的大分子，具有许多重要的细胞功能，从膜中的结构作用到信号传导和能量储存分子的功能。与其他大分子一样，脂质可能会被损坏（例如氧化），并且细胞需要质量控制系统来确保非功能性和潜在毒性的脂质不会积累。铁死亡是细胞死亡的一种形式，是由于脂质质量控制失败以及氧化损伤的磷脂随之积累而导致的。在这篇综述中，我们描述了脂质质量控制的框架，以铁死亡作为说明性例子，强调与脂质损伤、膜重塑以及通过先发制人和损伤修复脂质质量控制途径抑制或解毒脂质损伤相关的概念。 《生物化学年度评论》第 93 卷的在线出版日期为 2024 年 6 月。请参阅 http://www.annualreviews.org/page/journal/pubdates 了解修订后的估计。