School of Life and Environmental Sciences, Shaoxing University, Shaoxing City, Zhejiang, China.
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Cell Commun Signal. 2024 Oct 4;22(1):475. doi: 10.1186/s12964-024-01862-w.
Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.
过氧化物酶体是参与多种细胞过程的动态细胞器，包括脂质代谢、氧化还原平衡和细胞内代谢物转移。越来越多的证据表明，过氧化物酶体的动态平衡在人类健康和疾病中起着至关重要的作用，特别是在代谢紊乱和铁死亡中。过氧化物酶体的丰度和功能受到生物发生和降解途径之间复杂相互作用的调节，涉及过氧化物酶、膜蛋白和pexophagy。过氧化物酶体依赖性脂质代谢，特别是醚连接磷脂的合成，被认为可以调节细胞对铁死亡的敏感性，铁死亡是一种新发现的铁依赖性细胞死亡形式。本文讨论了过氧化物酶体动态平衡的最新认识，及其在氧化还原调节和脂质代谢中的作用，以及在人类疾病中的意义。我们还总结了铁死亡的主要机制，并强调了过氧化物酶体依赖性代谢和信号如何影响铁死亡敏感性的最新发现。更好地理解过氧化物酶体动态平衡和铁死亡之间的相互作用可能为疾病发病机制提供新的见解，并揭示与过氧化物酶体相关的代谢紊乱和铁死亡相关疾病的新治疗策略。
