A state-of-the-science review of using mitochondrial DNA copy number as a biomarker for environmental exposure

Mitochondria are bioenergetic, biosynthetic, and signaling organelles in eukaryotes, and contain their own genomes, mitochondrial DNA (mtDNA), to supply energy to cells by generating ATP via oxidative phosphorylation. Therefore, the threat to mitochondria' integrity and health resulting from environmental exposure could induce adverse health effects in organisms. In this review, we summarized the association between mtDNA copy number (mtDNAcn), and environmental exposures as reported in the literature. We conducted a literature search in the Web of Science using [Mitochondrial DNA copy number] and [Exposure] as two keywords and employed three selection criteria for the final inclusion of 97 papers for review. The consensus of data was that mtDNAcn could be used as a plausible biomarker for cumulative exposures to environmental chemical and physical agents. In order to furtherly expand the application of mtDNAcn in ecological and environmental health research, we suggested a series of algorithms aiming to standardize the calculation of mtDNAcn based on the PCR results in this review. We also discussed the pitfalls of using whole blood/plasma samples for mtDNAcn measurements and regard buccal cells a plausible and practical alternative. Finally, we recognized the importance of better understanding the mechanistic analysis and regulatory mechanism of mtDNAcn, in particular the signals release and regulation pathways. We believe that the development of using mtDNAcn as an exposure biomarker will revolutionize the evaluation of chronic sub-lethal toxicity of chemicals to organisms in ecological and environmental health research that has not yet been implemented.