Wāng Yán
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China.
Environ Int. 2025 Jan;195:109193. doi: 10.1016/j.envint.2024.109193. Epub 2024 Dec 12.
Fine particulate matter (PM2.5) is increasingly recognized for its detrimental effects on human health, with substantial evidence linking exposure to various forms of cell death and dysfunction across multiple organ systems. This review examines key cell death mechanisms triggered by PM2.5, including PANoptosis, necroptosis, autophagy, and ferroptosis, while other forms such as oncosis, paraptosis, and cuprotosis remain unreported in relation to PM2.5 exposure. Mitochondria, endoplasmic reticulum, and lysosomes emerge as pivotal organelles in the disruption of cellular homeostasis, with mitochondrial dysfunction particularly implicated in metabolic dysregulation and the activation of pro-apoptotic pathways. Although PM2.5 primarily affects the nucleus, cytoskeleton, mitochondria, endoplasmic reticulum, and lysosomes, other organelles like ribosomes, Golgi apparatus, and peroxisomes have received limited attention. Interactions between these organelles, such as endoplasmic reticulum-associated mitochondrial membranes, lysosome-associated mitophagy, and mitochondria-nuclei retro-signaling may significantly contribute to the cytotoxic effects of PM2.5. The mechanisms of PM2.5 toxicity, encompassing oxidative stress, inflammatory responses, and metabolic imbalances, are described in detail. Notably, PM2.5 activates the NLRP3 inflammasome, amplifying inflammatory responses and contributing to chronic diseases. Furthermore, PM2.5 exposure disrupts genetic and epigenetic regulation, often resulting in cell cycle arrest and exacerbating cellular damage. The composition, concentration, and seasonal variability of PM2.5 modulate these effects, underscoring the complexity of PM2.5-induced cellular dysfunction. Despite significant advances in understanding these pathways, further research is required to elucidate the long-term effects of chronic PM2.5 exposure, the role of epigenetic regulation, and potential strategies to mitigate its harmful impact on human health.
细颗粒物（PM2.5）对人类健康的有害影响日益受到认可，有大量证据表明，暴露于PM2.5会导致多个器官系统出现各种形式的细胞死亡和功能障碍。本综述探讨了由PM2.5引发的关键细胞死亡机制，包括PAN凋亡、坏死性凋亡、自噬和铁死亡，而诸如胀亡、副凋亡和铜死亡等其他形式与PM2.5暴露的关系尚未见报道。线粒体、内质网和溶酶体成为破坏细胞稳态的关键细胞器，线粒体功能障碍尤其与代谢失调和促凋亡途径的激活有关。尽管PM2.5主要影响细胞核、细胞骨架、线粒体、内质网和溶酶体，但核糖体、高尔基体和过氧化物酶体等其他细胞器受到的关注有限。这些细胞器之间的相互作用，如内质网相关线粒体膜、溶酶体相关线粒体自噬和线粒体-细胞核逆向信号传导，可能对PM2.5的细胞毒性作用有显著贡献。详细描述了PM2.5毒性的机制，包括氧化应激、炎症反应和代谢失衡。值得注意的是，PM2.5激活NLRP3炎性小体，放大炎症反应并导致慢性疾病。此外，暴露于PM2.5会破坏基因和表观遗传调控，常常导致细胞周期停滞并加剧细胞损伤。PM2.5的组成、浓度和季节变化会调节这些影响，突出了PM2.5诱导细胞功能障碍的复杂性。尽管在理解这些途径方面取得了重大进展，但仍需要进一步研究来阐明长期暴露于慢性PM2.5的影响、表观遗传调控的作用以及减轻其对人类健康有害影响的潜在策略。
