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

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

Cell reports (2020-03-12)
Miriam Hernández-Morales, Trisha Shang, Jingjia Chen, Victor Han, Chunlei Liu
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Capsaicin, ≥95%, from Capsicum sp.
Sigma-Aldrich
Ferritin from equine spleen, Type I, saline solution
Sigma-Aldrich
GSK1016790A, ≥98% (HPLC)
Sigma-Aldrich
Poly-L-lysine solution, mol wt 150,000-300,000, 0.01%, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder
Sigma-Aldrich
4-Hydroxynonenal, 4-Hydroxynonenal, CAS 75899-68-2, is a major aldehyde product formed by peroxidation of ω-6-unsaturated fatty acids that is regarded as a specific marker of lipid peroxidation.