MtDNA Copy Number in Oral Epithelial Cells Serves as a Potential Biomarker of Mitochondrial Damage by Neonicotinoid Exposure: A Cross-Sectional Study

Abstract

As the mitochondrial DNA copy number (mtDNAcn) has been reported to be a biomarker for mtDNA damage in honeybees when exposed to sublethal neonicotinoids, the feasibility of using human mitochondria as a predictor upon neonicotinoid exposure remains elusive. This study investigated the association between the urinary neonicotinoid and the relative mtDNAcn (RmtDNAcn) of oral epithelial cells collected in a cross-sectional study with repeated measurements over 6 weeks. The molecular mechanism underlying neonicotinoid-caused mitochondrial damage was also examined by in vitro assay. Herein, the average integrated urinary neonicotinoid (IMIRPF) concentration ranged from 8.01 to 13.70 μg/L (specific gravity-adjusted) during the sampling period. Concomitantly, with an increase in the urinary IMIRPF, the RmtDNAcn significantly increased from 1.20 (low group) to 1.93 (high group), indicating potential dose-dependent mitochondrial damage. Furthermore, the linear regression analysis confirmed the significant correlation between the IMIRPF and RmtDNAcn. Results from in vitro assays demonstrated that neonicotinoid exposure led to the inhibition of the genes encoding mitochondrial oxidative phosphorylation (OXPHOS) complexes I and III (e.g., ND2, ND6, CytB, and CYC1), accompanied by increased reactive oxygen species production in SH-SY5Y cells. Conjointly, neonicotinoid exposure led to mitochondrial dysfunction and a resulting increase in the RmtDNAcn, which may serve as a plausible biomarker in humans.

Exploring mitochondrial DNA copy number in circulating cell‐free DNA and extracellular vesicles across cardiovascular health status: A prospective case–control pilot study

“…It consists of 16 569 base pairs, and it contains 37 genes: 13 encoding for oxidative phosphorylation mRNAs, 22 for tRNAs, and 2 for rRNAs 1 . MtDNA exists in cells in a different copy number (mtDNAcn) depending on the tissue type, health status of cells or environmental exposures 2‐13 . Also, increasing evidence demonstrated the presence of mtDNA in body fluids as circulating cell‐free mtDNA (ccf‐mtDNA) 14 .…”

“…1 MtDNA exists in cells in a different copy number (mtDNAcn) depending on the tissue type, health status of cells or environmental exposures. [2][3][4][5][6][7][8][9][10][11][12][13] Also, increasing evidence demonstrated the presence of mtDNA in body fluids as circulating cell-free mtDNA (ccf-mtDNA). 14 Ccf-mtDNA can circulate in body fluids as naked or contained in lipid-based vesicles.…”