Cuproptosis是一种新型的铜诱导的细胞死亡方式，主要发生在利用氧化磷酸化作为主要代谢途径产生能量的细胞中。铜直接与三羧酸循环的脂砜化蛋白结合，导致这些脂砜化蛋白发生二硫化物键依赖性聚集，使铁硫簇蛋白不稳定并引起蛋白质毒性应激。癌细胞更喜欢通过糖酵解（沃尔堡效应）产生中间代谢物和能量，从而实现对Cuproptosis的抵抗。有趣的是，肿瘤抑制因子p53是一个关键的代谢调节因子，它抑制糖酵解并驱动代谢转换朝着氧化磷酸化的方向进行。此外，p53还调节铁硫簇生物合成和铜螯合剂谷胱甘肽的合成，这两个因素是Cuproptotic途径中的两个关键组成部分，这表明这个肿瘤抑制因子可能在Cuproptosis中发挥作用。此外，还讨论了突变的p53在调节Cuproptosis中的可能作用。本文回顾了Cuproptosis机制的最新进展，并重新审视了p53在代谢调节、铁硫簇和谷胱甘肽生物合成中的作用，并提出了几种潜在的机制，用于调节野生型和突变型p53介导的Cuproptosis调控。©2023年，作者（们）发表。

Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a metabolic switch towards oxidative phosphorylation in cancer cells. Additionally, p53 regulates the biogenesis of iron-sulfur clusters and the copper chelator glutathione, which are two critical components of the cuproptotic pathway, suggesting that this tumor suppressor might play a role in cuproptosis. Furthermore, the possible roles of mutant p53 in regulating cuproptosis are discussed. In this essay, we review the recent progress in the understanding of the mechanism underlying cuproptosis, revisit the roles of p53 in metabolic regulation and iron-sulfur cluster and glutathione biosynthesis, and propose several potential mechanisms for wild-type and mutant p53-mediated cuproptosis regulation.© 2023. The Author(s).