Abstract
Mitochondria are cellular organelles that play an important role in cellular energy production, signaling, differentiation, and apoptosis. All organisms are believed to have low levels of variation in mitochondrial DNA (mtDNA), and repeated mitotic segregation and clonal expansion can enable a mitochondrion to eventually dominate the mtDNA pool. Alterations in mtDNA are connected to a range of human diseases. Therefore, understanding how changes in mtDNA accumulate over time and are correlated to changes in mitochondrial function can have a profound impact on our understanding of fundamental cell biophysics and the origins of some human diseases. Motivated by this, we develop and study a mathematical model to determine which cellular parameters have the largest impact on mtDNA population dynamics. The model consists of coupled differential equations to describe populations of healthy and dysfunctional mitochondria subject to mitochondrial fission, fusion, autophagy, and varying levels of cellular ATP. We study the time evolution of each population under specific selection biases and obtain a heat map in the parameter space of the ratio of the rates of fusion and autophagy of the healthy and dysfunctional populations. Our results may provide insights into how different mitochondrial populations survive and evolve under different selection pressures and with time.
Highlights
Mitochondria are organelles located inside eukaryotic cells and are famously known as the powerhouse of the cell because of their role in energy (ATP) production
Assuming selection pressures that lead to healthy mitochondria fusing at higher rates than unhealthy mitochondria while the latter is removed from the cell at a higher rate, one would expect mitochondrial populations to consists of significantly higher concentrations of healthy mitochondria at long times
We have studied a minimal ODE model to examine how the population dynamics of cellular mtDNA is influenced by variations in the rates of mitochondrial fission, fusion, mitophagy, and cellular ATP levels, and their interplay
Summary
Mitochondria are organelles located inside eukaryotic cells and are famously known as the powerhouse of the cell because of their role in energy (ATP) production. The model consists of coupled ODEs to describe populations of healthy and dysfunctional (unhealthy) mitochondria subject to mitochondrial fission, fusion, mitophagy, and varying levels of cellular ATP, which depend on ATP production by mitochondria and energy use during mitochondrial dynamics and other physiological processes [18].
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