The Impact of Exogenous Mutagens on Human Mitochondrial DNA Ploidy: Analysis of Changes and Possible Protective Mechanisms.

Abstract

Mitochondrial ploidy -- the relative copy number of mitochondrial DNA per mitochondrion -- may serve as an early marker of cellular stress and a potential signal of genotoxic damage. In this study, we investigate the dynamics of mitochondrial ploidy in iPSC cells in vitro following exposure to a range of chemical mutagens. Using a qPCR-based method allowing accurate quantification of mitochondrial DNA and mitochondria number, we reveal distinct changes in mitochondrial ploidy that correlate with the genotoxic impact of specific agents. Among the mutagens tested, MX, benzidine, cyclophosphamide, hydrogen peroxide, semustine and nickel (II) chloride induced the most pronounced alterations in mitochondrial DNA content and organization. These findings suggest that mitochondrial ploidy can be used as a sensitive molecular indicator of mutagenic stress, potentially reflecting mitochondrial genome maintenance and organelle adaptation mechanisms.