Predictability of environment-dependent formation of G-quadruplex DNAs in human mitochondria

Molecular crowding affects the stability of nucleic acids (DNA and RNA) and induces their non-canonical structures. As the level of molecular crowding varies spatio-temporally in cells, it would be beneficial to predict the behaviour of DNA and RNA structures depending on the local cellular environments. This has applications in human mitochondria, which possess an especially crowded condition. In this study, the predictability of guanine-quadruplex (G4) DNA formation in the environment specific to human mitochondria was investigated. In accordance with the stability of duplexes predicted by our nearest-neighbour parameters, the G-rich duplex stability was found to effectively decrease and G4 formation was induced in mitochondrion-like conditions compared to the nucleus-like conditions. Using a peptide-based mitochondrial targeting system, a G4 reporter assay performed in mitochondria indicated that G4 formation were more favoured in mitochondria more than in the nucleus. These findings provide insights useful for the prediction of the behaviour of nucleic acids in mitochondria.