# Extremely low-frequency electromagnetic field (ELF-EMF) enhances mitochondrial energy production in NARP cybrids

## TL;DR

Exposure to extremely low-frequency electromagnetic fields improves mitochondrial energy production in cells with a mitochondrial DNA mutation linked to NARP syndrome.

## Contribution

This study reveals that ELF-EMF enhances mitochondrial function in NARP cybrids through transcriptional and biochemical changes.

## Key findings

- ELF-EMF increased mtDNA transcription and wild-type-to-mutant transcription ratio in NARP cybrids.
- ELF-EMF upregulated OXPHOS proteins and Complex V activity in NARP cybrids.
- ELF-EMF boosted ATP production and altered mitochondrial dynamics in NARP cybrids.

## Abstract

A mutation (m.8993T > G) in MT-ATP6 in mitochondrial DNA (mtDNA) causes the neuropathy, ataxia, retinitis pigmentosa (NARP) syndrome by impairing mitochondrial energy production. Extremely low-frequency electromagnetic field (ELF-EMF) suppresses mitochondrial oxidative phosphorylation (OXPHOS) Complex II and induces mitohormetic activation of mitochondrial OXPHOS activities. We examined the effects of ELF-EMF on normal cybrids carrying 100% wild-type mtDNA (2SA cybrids) and NARP cybrids carrying 40% wild-type and 60% mutant mtDNA (NARP3-2 cybrids). We found that ELF-EMF had no effect on the copy number of mtDNA either in 2SA or NARP3-2 cybrids, or the ratio of wild-type-to-mutant mtDNA in NARP3-2 cybrids. Instead, ELF-EMF increased the transcription of mtDNA and the transcription ratio of wild-type-to-mutant mtDNA in NARP3-2 cybrids. In addition, ELF-EMF increased the expression of mitochondrial OXPHOS proteins and the mitochondrial OXPHOS Complex V activity in NARP3-2 cybrids. ELF-EMF upregulated fission-promoting phosphorylation of DRP1, as well as the expression of fusion-promoting MFN1 and MFN2, in NARP3-2 cybrids. ELF-EMF also increased ATP production estimated by oxygen consumption rates (OCR) and by a biochemical assay in NARP3-2 cybrids. Hormetic activation of mitochondria by ELF-EMF is likely to be effective to ameliorate defective mitochondrial energy production in NARP and other mitochondrial diseases.

The online version contains supplementary material available at 10.1038/s41598-025-10536-7.