Lipid oxidation induced by RF fields and mediated by ferritin iron causes activation of ferritin-tagged ion channels. Hernández-Morales et al.
Using the FeRIC (Ferritin iron Redistribution to Ion Channels) system, we have uncovered a mechanism of activation of ferritin-tagged channels via a biochemical pathway initiated by RF disturbance of ferritin and mediated by ferritin-associated iron. We show that in cells expressing TRPVFeRIC channels, RF increases the levels of the labile iron pool in a ferritin-dependent manner. Free iron participates in chemical reactions producing reactive oxygen species and oxidized lipids that ultimately activate the TRPVFeRIC channels. This biochemical pathway predicts a similar RF-induced activation of other lipid-sensitive TRP channels and may guide future magnetogenetic designs. Data correspond to the statistical analysis of the responsiveness in cells expressing FeRIC channels stimulated with radiofrequency magnetic fields in different experimental conditions. All experiments have repeated a minimum of three times. Differences in continuous data sets were analyzed using Microcal OriginPro 2020 software (OriginLab). For statistical comparison of the fraction of cells responsive to RF or lipids, each cell was binarily labeled. Responsive cells were assigned with the value 1 and non-responsive cells were assigned with the value 0. Next, for each experimental group, the binary data from all the independent experiments were grouped and the hypothesis testing was performed using the nonparametric Kruskal-Wallis ANOVA followed by Dunn's multiple comparisons test. Data are means ± SEM, where applicable p<0.05, p<0.001, or p<0.0001 was considered a statistically significant difference.