Lipid Oxidation Induced by RF Waves and Mediated by Ferritin Iron Causes Activation of Ferritin-Tagged Ion Channels

Abstract

Summary: One approach to magnetogenetics uses radiofrequency (RF) waves to activate transient receptor potential channels (TRPV1 and TRPV4) that are coupled to cellular ferritins. The mechanisms underlying this effect are unclear and controversial. Theoretical calculations suggest that the heat produced by RF fields is likely orders of magnitude weaker than needed for channel activation. 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. : Radio-frequency (RF) fields activate TRPV channels coupled to endogenous ferritins. Hernández-Morales et al. show that ferritins transduce RF into biochemical signals responsible for channel activation. The interaction between RF and ferritin causes the increase of free iron, reactive oxygen species, and oxidized lipids, all of them TRPV actuators. Keywords: magnetic control, magnetogenetics, ferritin, TRPV channels, cytosolic Ca2+ concentration, radiofrequency magnetic fields, reactive oxygen species, lipid oxidation, labile iron pool