Polg2, polymerase (DNA directed), gamma 2, accessory subunit, is part of the mitochondrial DNA polymerase gamma holoenzyme, crucial for mitochondrial DNA (mtDNA) replication and maintenance [1,2,3,4]. It forms a dimeric accessory subunit that confers processivity to the catalytic subunit POLG, and is involved in pathways related to mitochondrial function, which is of great biological importance for cell energy production and overall organism function. Genetic models, like the zebrafish model, are valuable for studying Polg2 [1].

In zebrafish, a polg2 mutant line generated by Nuclease technology technology showed slower development, decreased viability, and phenotypes similar to human POLG-related diseases, including mtDNA depletion, altered mitochondrial network and dynamics, reduced mitochondrial respiration, morphological alterations in high-energy demanding tissues, and decreased larval motility. Treatment with Clofilium tosylate could partially rescue mtDNA depletion in these mutants [1]. In mice, Polg2-/-embryos were embryonic lethal at day 8.0-8.5 p.c., with loss of mtDNA and mtDNA gene products, and severe mitochondrial ultra-structural defects [4].

In conclusion, Polg2 is essential for mammalian embryogenesis and mtDNA replication. Model-based research, such as the zebrafish and mouse models, has revealed its critical role in maintaining normal mitochondrial function and development. These models contribute to understanding the etiopathology of human POLG-related disorders associated with Polg2 mutations, which may help in developing treatments for such mitochondrial diseases [1,4].