Dynamics of mtDNA populations in mammalian cells: role of mitochondrial dynamics and its interplay with mitochondrial membrane potential*

Mitochondria are organelles found in almost all eukaryotic cells. They are highly dynamic and once formed, they can undergo changes in size and content via the processes of fusion, fission, and mitophagy. Mitochondria are famously known as the powerhouse of the cell for their role in cellular energy production. They are also essential for cell signaling and apoptosis, and have their own DNA, called mtDNA, which is maternally inherited. The same cell can have multiple variants of mtDNA, and harmful alterations in mtDNA can accumulate over time resulting in pathological changes in mitochondrial function and disease states. We develop and study a mathematical model to understand and predict the population dynamics of mtDNA and how it is correlated to changes in mitochondrial bioenergetics. We examine the spatiotemporal evolution of populations of healthy and dysfunctional mitochondria subject to mitochondrial biogenesis, fission, fusion, mitophagy, and changes in the mitochondrial membrane potential, and determine their relative impact on mtDNA population dynamics. Our results may provide insights into how different mtDNA populations survive and evolve under different selection pressures and the origins of mtDNA disorders.