https://doi.org/10.1016/j.apsb.2025.10.027
This new article publication from Acta Pharmaceutica Sinica B, discusses how palmitoylation of Tfr1 enhances platelet ferroptosis and liver injury in heat stroke.
Heat stroke (HS) is a severe medical emergency characterized by coagulation and high mortality due to organ injury. This study identifies a novel mechanism in which platelet ferroptosis, driven by transferrin receptor 1 (Tfr1) palmitoylation, significantly contributes to liver injury in HS. The findings reveal a strong inverse correlation between platelet count and organ damage, especially liver injury, as well as mortality rates. Using murine models, it was demonstrated that inhibiting Tfr1-mediated ferroptosis in platelets mitigates thrombocytopenia and decreases Interleukin-1β (IL-1β) secretion, thereby improving liver function and survival outcomes. This research highlights Tfr1 palmitoylation as a critical factor in iron transport within platelets, with the palmitoylation inhibitor 2-bromopalmitate (2BP) effectively reducing total iron, Fe2+, lipid ROS, 4-hydroxynonenal (4-HNE), and cell cytotoxicity under heat stress. These results suggest that targeting Tfr1 palmitoylation-dependent ferroptosis in platelets offers a novel therapeutic strategy for treating HS-induced thrombocytopenia and liver injury.
Keywords: Heat stroke, Heat stroke-induced liver injury, Platelet, Ferroptosis, Tfr1, Palmitoylation, Cytokines, IL-1β
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525007051-ga1_lrg.jpg
Tfr1 palmitoylation-mediated ferroptosis in platelets, accompanied by IL-1β secretion, exacerbates liver injury in HS. The findings provide novel insights into thrombocytopenia and liver injury in HS, offering a potential therapeutic strategy to mitigate HS-induced thrombocytopenia, liver injury, and poor prognosis.
