Rockfield Stephanie, Chhabra Ravneet, Robertson Michelle, Rehman Nabila, Bisht Richa, Nanjundan Meera
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA.
Pharmaceuticals (Basel). 2018 Oct 22;11(4):113. doi: 10.3390/ph11040113.
Maintenance of iron homeostasis is critical to cellular health as both its excess and insufficiency are detrimental. Likewise, lipids, which are essential components of cellular membranes and signaling mediators, must also be tightly regulated to hinder disease progression. Recent research, using a myriad of model organisms, as well as data from clinical studies, has revealed links between these two metabolic pathways, but the mechanisms behind these interactions and the role these have in the progression of human diseases remains unclear. In this review, we summarize literature describing cross-talk between iron and lipid pathways, including alterations in cholesterol, sphingolipid, and lipid droplet metabolism in response to changes in iron levels. We discuss human diseases correlating with both iron and lipid alterations, including neurodegenerative disorders, and the available evidence regarding the potential mechanisms underlying how iron may promote disease pathogenesis. Finally, we review research regarding iron reduction techniques and their therapeutic potential in treating patients with these debilitating conditions. We propose that iron-mediated alterations in lipid metabolic pathways are involved in the progression of these diseases, but further research is direly needed to elucidate the mechanisms involved.
维持铁稳态对细胞健康至关重要,因为铁过量和不足均有害。同样,作为细胞膜的重要组成部分和信号传导介质的脂质,也必须受到严格调控以阻碍疾病进展。最近,利用多种模式生物进行的研究以及临床研究数据,揭示了这两种代谢途径之间的联系,但这些相互作用背后的机制以及它们在人类疾病进展中的作用仍不清楚。在本综述中,我们总结了描述铁和脂质途径之间相互作用的文献,包括铁水平变化时胆固醇、鞘脂和脂滴代谢的改变。我们讨论了与铁和脂质改变相关的人类疾病,包括神经退行性疾病,以及关于铁可能促进疾病发病机制的潜在机制的现有证据。最后,我们回顾了关于铁还原技术及其在治疗这些衰弱病症患者方面的治疗潜力的研究。我们提出,铁介导的脂质代谢途径改变参与了这些疾病的进展,但迫切需要进一步研究以阐明其中涉及的机制。