Mitochondrial proteome evolution and genetic disease

  • Huynen M
  • de Hollander M
  • Szklarczyk R
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Abstract

Mitochondria are an essential organelle, not only to the human cell, but to all eukaryotic life. This essentiality is reflected in the large number of mutations in genes encoding mitochondrial proteins that lead to disease. Aside from their relevance to disease, mitochondria are, given their endosymbiotic origin, very interesting from an evolutionary point of view. Here, in the year that marks the bicentenary of Darwin's birth and the 150th anniversary of the publication of "On the origin of species" we review approaches that implicitly or explicitly use evolutionary analyses to find new genes involved in mitochondrial disease and to predict their function and involvement in pathways. We show how the phenotypic spectrum of mitochondrial disease is linked to the evolutionary origin of mitochondrial proteins, how combinations of evolutionary data and genomics data have been used to predict the mitochondrial proteome and functional links between the mitochondrial proteins and how the evolution of the mitochondrial proteome has been used to predict new mitochondrial disease genes. For the latter we review and reanalyze the eukaryotic evolution of the NADH:ubiquinone oxidoreductase (complex I) and the proteins involved in its assembly.

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Authors

  • Martijn A. Huynen

  • Mattias de Hollander

  • Radek Szklarczyk

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