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FALCON-qPCR: a new method for the quantification of oxidative lesions in mitochondrial DNA

Title: FALCON-qPCR: a new method for the quantification of oxidative lesions in mitochondrial DNA
Authors: Veronica Bazzani; Eve Harding; Szymon Balinski; Mara Equisoain Redina; Dario Alessi; Pierfrancesco Del Mestre; Walter Baratta; Daniela Cesselli; Antonio Paolo Beltrami; Michał Turek; Umberto Baccarani; Carlo Vascotto
Contributors: Bazzani, Veronica; Harding, Eve; Balinski, Szymon; Equisoain Redina, Mara; Alessi, Dario; Del Mestre, Pierfrancesco; Baratta, Walter; Cesselli, Daniela; Beltrami, Antonio Paolo; Turek, Michał; Baccarani, Umberto; Vascotto, Carlo
Publication Year: 2026
Collection: Università degli Studi di Udine: CINECA IRIS
Subject Terms: Mitochondria; mitochondrialDNA damage; oxidativestre; LongRange-PCR
Description: Accurate quantification of oxidative mitochondrial DNA (mtDNA) lesions remains technically challengingdue to the limitations of existing assays, which often require large sample inputs, multi-day workflows,and offer limited sensitivity. Here we introduce FALCON-qPCR (Fpg-assisted Long-PCR), a streamlined,high-sensitivity method for quantifying oxidative damage in mtDNA. FALCON-qPCR couples digestionwith formamidopyrimidine [fapy]-DNA glycosylase (Fpg) to long-range PCR and qPCR-based normal-ization, enabling precise lesion quantification from as few as 10,000 cells (~300 ng total DNA) withina single day. The assay provides a robust dynamic range and reproducibility across diverse biologicalsystems, including human cell lines, hepatocellular carcinoma biopsies, and Caenorhabditis elegans.Compared with established methods, FALCON-qPCR exhibits markedly higher sensitivity in detectingmtDNA damage induced by hydrogen peroxide, antimycin A, and rotenone. Its performance was furtherdemonstrated in assessing mitochondrial toxicity of ruthenium-based compounds, highlighting its poten-tial for pharmacological screening. By integrating enzymatic lesion recognition with quantitative ampli-fication in a unified workflow, FALCON-qPCR eliminates the need for mitochondrial isolation. Thismethodological advance provides a rapid, accurate, and scalable platform for studying oxidative DNAdamage, with broad applicability in mitochondrial research and translational toxicology.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/wos/WOS:001660565300001; volume:17; issue:24; firstpage:1671; lastpage:1683; numberofpages:13; journal:BIOANALYSIS; https://hdl.handle.net/11390/1322064
DOI: 10.1080/17576180.2025.2608757
Availability: https://hdl.handle.net/11390/1322064; https://doi.org/10.1080/17576180.2025.2608757
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.B4125BF2
Database: BASE