PerspectiveGenetics

Mitochondrial-nuclear DNA mismatch matters

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Science  25 Sep 2015:
Vol. 349, Issue 6255, pp. 1449-1450
DOI: 10.1126/science.aac5271

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Summary

Diseases caused by pathogenic mutations in mitochondrial DNA (mtDNA) often lead to severe, multisystem complications and death during childhood or adolescence, and in some cases, adult onset can lead to premature death. Researchers have proposed techniques to prevent the transmission of mtDNA disease through mtDNA replacement therapies that involve combining healthy nuclear and mtDNA from three individuals. This past February, the United Kingdom became the first country to legalize mtDNA replacement (the United States continues to consider the ethical and social implications). Although mitochondrial and nuclear genomes are physically separate in the cell, they work together functionally to control various metabolic and developmental processes, including energy production, cell growth, programmed cell death, and thermogenesis. This intergenomic relationship raises questions about possible effects of different mtDNAs (those that are not the original mtDNAs in a given cell) on cellular bioenergetics and disease susceptibility (see the figure). Recent studies in mice that have examined this issue suggest that different mtDNA and nuclear DNA combinations could plausibly have differential effects on gene expression and cell function.