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Cell Rep. 2020 Mar 10;30(10):3250-3260.e7. doi: 10.1016/j.celrep.2020.02.070.

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

Author information

1
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
2
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
3
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.
4
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: chunlei.liu@berkeley.edu.

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.

KEYWORDS:

TRPV channels; cytosolic Ca(2+) concentration; ferritin; labile iron pool; lipid oxidation; magnetic control; magnetogenetics; radiofrequency magnetic fields; reactive oxygen species

PMID:
32160534
DOI:
10.1016/j.celrep.2020.02.070
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Conflict of interest statement

Declaration of Interests C.L. shares ownership of a patent application (WO2016004281 A1 PCT/US2015/038948) relating to the use of FeRIC for cell modulation and treatments. All other authors declare that they have no competing interests.

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