The journal of physical chemistry. BMay 31, 2018

Linking Light Activation of Fruit Fly Cryptochrome to Oxidation of a Potassium Channel Cofactor

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Updated Feb 22, 2026

Abstract

The oxidation of NADPH by TRP or HO is thermodynamically feasible.

Light-induced processes in Drosophila's cryptochrome may regulate neuronal firing rates.
A radical pair formed in cryptochrome could facilitate the transfer of electrons to oxidize NADPH.
The oxidation of NADPH may lead to the inhibition of inactivation in the voltage-dependent Kchannel.
Another proposed pathway involves the reoxidation of cryptochrome's FAD by molecular oxygen, producing hydroxyl radicals that could also oxidize NADPH.
These findings may contribute to understanding a potential magnetic sensing signal transduction pathway in Drosophila.

Simplified

Motivated by the observations on the involvement of light-induced processes in the Drosophila melanogaster cryptochrome (DmCry) in regulation of the neuronal firing rate, which is achieved by a redox-state change of its voltage-dependent Kchannel Kvβ subunit hyperkinetic (Hk) reduced nicotinamide adenine dinucleotide phosphate (NADPH) cofactor, we propose in this work two hypothetical pathways that may potentially enable such coupling. In the first pathway, triggered by blue-light-induced formation of a radical pair [FADTRP] in DmCry, the hole (TRP) may hop to Hk, for example, through a tryptophan chain and oxidize NADPH, possibly leading to inhibition of the N-terminus inactivation in the Kchannel. In a second possible pathway, DmCry's FADis reoxidized by molecular oxygen, producing HO, which then diffuses to Hk and oxidizes NADPH. In this work, by applying a combination of quantum and empirical-based methods for free-energy calculations, we find that the oxidation of NADPH by TRPor HOand the reoxidation of FADby Oare thermodynamically feasible. Our results may have an implication in identifying a magnetic sensing signal transduction pathway, specifically upon Drosophila's Hk NADPH cofactor oxidation, with a subsequent inhibition of the Kchannel N-terminus inactivation gate, permitting Kflux. + •-•+ •+ + •-•+ •-+ + 2 2 2 2 2

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Linking Light Activation of Fruit Fly Cryptochrome to Oxidation of a Potassium Channel Cofactor

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