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

• DOI: 10.1016/j.celrep.2020.02.070
• Publication Date: 2020-03-10T15:11:27Z
• Authors: Miriam Hernández-...; Trisha Shang; Jingjia Chen; Victor Han; Chunlei Liu
• Keywords: 0301 basic medicine; 571; magnetic control; 572; QH301-705.5; Radio Waves; Iron; Medical Physiology; labile iron pool; TRPV Cation Channels; Ion Channels; Cell Line; Mice; 03 medical and health sciences; Cytosol; lipid oxidation; Animals; Humans; cytosolic Ca(2+) concentration; Biology (General); magnetogenetics; reactive oxygen species; ferritin; Temperature; radiofrequency magnetic fields; Biological Sciences; Lipid Metabolism; Biological sciences; Ferritins; Calcium; TRPV channels; Biochemistry and Cell Biology; Reactive Oxygen Species; Ion Channel Gating; Oxidation-Reduction

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.