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Review
. 2019 Jun 18;8(6):608.
doi: 10.3390/cells8060608.

Mitochondrial DNA Variants and Common Diseases: A Mathematical Model for the Diversity of Age-Related mtDNA Mutations

Huanzheng Li  1   2 , Jesse Slone  3 , Lin Fei  4 , Taosheng Huang  5
Affiliations
Review

Mitochondrial DNA Variants and Common Diseases: A Mathematical Model for the Diversity of Age-Related mtDNA Mutations

Huanzheng Li et al. Cells. .

Abstract

The mitochondrion is the only organelle in the human cell, besides the nucleus, with its own DNA (mtDNA). Since the mitochondrion is critical to the energy metabolism of the eukaryotic cell, it should be unsurprising, then, that a primary driver of cellular aging and related diseases is mtDNA instability over the life of an individual. The mutation rate of mammalian mtDNA is significantly higher than the mutation rate observed for nuclear DNA, due to the poor fidelity of DNA polymerase and the ROS-saturated environment present within the mitochondrion. In this review, we will discuss the current literature showing that mitochondrial dysfunction can contribute to age-related common diseases such as cancer, diabetes, and other commonly occurring diseases. We will then turn our attention to the likely role that mtDNA mutation plays in aging and senescence. Finally, we will use this context to develop a mathematical formula for estimating for the accumulation of somatic mtDNA mutations with age. This resulting model shows that almost 90% of non-proliferating cells would be expected to have at least 100 mutations per cell by the age of 70, and almost no cells would have fewer than 10 mutations, suggesting that mtDNA mutations may contribute significantly to many adult onset diseases.

Keywords: aging; cancer; diabetes; mitochondria; mitochondrial genetics; mutation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simulated distribution of mutations per proliferating cell at the age of 70.
Figure 2
Figure 2
Reversed cumulative distribution of mutations per cell at the age of 70.
See this image and copyright information in PMC

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