DEVELOPMENT OF A CLASSIFICATION FOR MITOCHONDRIAL MUTAGENS: ANALYSIS OF THE CHEMICAL NATURE OF MUTAGENS AND THEIR FUNCTIONAL PROPERTIES

Van Leiden Nikita Sergeevich, Patlay Nataliya Igorevna, Park Sochee

Mitochondrial dysfunction may be associated with damage to mitochondrial DNA (mtDNA) by mutagens [1]. However, the mutational signatures of both individual mutagens and their groups have not been established; therefore, the issue of creating a classification of mtDNA mutagens according to the functional principle and the chemical nature of origin is topical. In this article, the mutagens used in the works of Serena Nik-Zainal [2, 3] were analyzed and a new classification system was proposed that takes into account physiological and structural features. Three main groups of mutagens were identified according to their functional effect on mtDNA: oxidative stress initiators, adductors, and alkylating agents. We hypothesize that many mitochondrial mutagens damage mtDNA indirectly through the generation of large amounts of reactive oxygen species (ROS). Adduct formers are mainly represented by polycyclic aromatic hydrocarbons, which irreversibly bind to mtDNA. Presumably, some mutagens are able to act as superoxide dismutase inhibitors, causing an abnormal increase in the number of mutations. Funding: This research was supported by funds provided through the Russian Federal Academic Leadership Program “Priority 2030” at the Immanuel Kant Baltic Federal University, project number 1166.

Keywords:mitochondria, mitochondrial DNA, mutagenesis, reactive oxygen species, oxidative stress