When growing cells double in size, they need to ensure that also the amount of their DNA doubles. To achieve this, replication of nuclear DNA is coupled to cell cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mtDNA replication is not strictly coupled to the cell cycle and can occur throughout the cell cycle and even continue during long cell cycle arrests. How do cells ensure then that they produce the right amount of mtDNA? We found that mtDNA copy number increases with cell volume, which ensures constant concentrations. This coupling of mtDNA to cell volume is achieved through limiting components of the mtDNA replication and maintenance machinery that are encoded by the nuclear genome and increase in abundance as cells increase in size.

Seel, A., Padovani, F., Mayer, M., Finster, A., Bureik, D., Thoma, F., Osman, C., Klecker, T. & Schmoller, K.M. (2023) Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth, Nature Structural & Molecular Biology