脂质过氧化
生物
细胞生物学
疟原虫(生命周期)
GPX4
细胞凋亡
活性氧
代谢途径
平衡
寄生虫寄主
生物化学
谷胱甘肽
抗氧化剂
新陈代谢
酶
万维网
计算机科学
谷胱甘肽过氧化物酶
作者
Heather S. Kain,Elizabeth K.K. Glennon,Kamalakannan Vijayan,Nadia Arang,Alyse N. Douglass,Chelsea L. Fortin,Meghan Zuck,Adam Lewis,Samantha Whiteside,Denali R. Dudgeon,Jarrod S Johnson,Alan Aderem,Kelly R. Stevens,Alexis Kaushansky
标识
DOI:10.1038/s41418-019-0338-1
摘要
The facets of host control during Plasmodium liver infection remain largely unknown. We find that the SLC7a11-GPX4 pathway, which has been associated with the production of reactive oxygen species, lipid peroxidation, and a form of cell death called ferroptosis, plays a critical role in control of Plasmodium liver stage infection. Specifically, blocking GPX4 or SLC7a11 dramatically reduces Plasmodium liver stage parasite infection. In contrast, blocking negative regulators of this pathway, NOX1 and TFR1, leads to an increase in liver stage infection. We have shown previously that increased levels of P53 reduces Plasmodium LS burden in an apoptosis-independent manner. Here, we demonstrate that increased P53 is unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of ROS scavenging or when lipid peroxidation is blocked. Additionally, SLC7a11 inhibitors Erastin and Sorafenib reduce infection. Thus, blocking the host SLC7a11-GPX4 pathway serves to selectively elevate lipid peroxides in infected cells, which localize within the parasite and lead to the elimination of liver stage parasites.
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