Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, South Korea.
Department of Biological Sciences, College of Natural Science, Seoul National University, Seoul, 08826, South Korea.
Exp Mol Med. 2023 Aug;55(8):1632-1643. doi: 10.1038/s12276-023-01069-y. Epub 2023 Aug 23.
Pyroptosis, apoptosis, necroptosis, and ferroptosis, which are the most well-studied regulated cell death (RCD) pathways, contribute to the clearance of infected or potentially neoplastic cells, highlighting their importance in homeostasis, host defense against pathogens, cancer, and a wide range of other pathologies. Although these four RCD pathways employ distinct molecular and cellular processes, emerging genetic and biochemical studies have suggested remarkable flexibility and crosstalk among them. The crosstalk among pyroptosis, apoptosis and necroptosis pathways is more evident in cellular responses to infection, which has led to the conceptualization of PANoptosis. In this review, we provide a brief overview of the molecular mechanisms of pyroptosis, apoptosis, necroptosis, and ferroptosis and their importance in maintaining homeostasis. We discuss the intricate crosstalk among these RCD pathways and the current evidence supporting PANoptosis, focusing on infectious diseases and cancer. Understanding the fundamental processes of various cell death pathways is crucial to inform the development of new therapeutics against many diseases, including infection, sterile inflammation, and cancer.
细胞焦亡、细胞凋亡、细胞坏死和铁死亡是研究最深入的调控性细胞死亡（RCD）途径，它们有助于清除感染或潜在的肿瘤细胞，突出了它们在维持体内平衡、宿主防御病原体、癌症以及广泛的其他病理学中的重要性。尽管这四种 RCD 途径采用不同的分子和细胞过程，但新兴的遗传和生化研究表明它们之间存在显著的灵活性和串扰。细胞焦亡、细胞凋亡和细胞坏死途径之间的串扰在细胞对感染的反应中更为明显，这导致了 PANoptosis 的概念化。在这篇综述中，我们简要概述了细胞焦亡、细胞凋亡、细胞坏死和铁死亡的分子机制及其在维持体内平衡中的重要性。我们讨论了这些 RCD 途径之间复杂的串扰以及支持 PANoptosis 的当前证据，重点关注传染病和癌症。了解各种细胞死亡途径的基本过程对于开发针对许多疾病（包括感染、无菌性炎症和癌症）的新疗法至关重要。
