Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA; email:
Department of Molecular and Cell Biology, University of California, Berkeley, California, USA; email:
Annu Rev Biochem. 2024 Aug;93(1):499-528. doi: 10.1146/annurev-biochem-052521-033527. Epub 2024 Jul 2.
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.
细胞质量控制系统感知并介导体内平衡反应，以防止异常大分子的积累，这些大分子是由于生物合成过程中的错误、环境损伤、酶和代谢活性失衡而产生的。脂质是结构多样的大分子，具有许多重要的细胞功能，从膜的结构作用到信号和能量储存分子的功能。与其他大分子一样，脂质可能会受到损伤（例如，氧化），细胞需要质量控制系统来确保无功能和潜在有毒的脂质不会积累。铁死亡是一种细胞死亡形式，它是由于脂质质量控制的失败和由此产生的氧化损伤磷脂的积累而导致的。在这篇综述中，我们描述了一个脂质质量控制的框架，使用铁死亡作为一个说明性的例子，强调与脂质损伤、膜重塑以及通过预先防范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。
