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Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10154-61. doi: 10.1073/pnas.1421372112. Epub 2015 Jul 20.

Mitochondrial genomes are retained by selective constraints on protein targeting.

Author information

1
Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden;
2
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520.
3
Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden; Siv.Andersson@icm.uu.se.

Abstract

Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome.

KEYWORDS:

endoplasmatic reticulum; evolution; mitochondria; protein domain; signal recognition particle

PMID:
26195779
PMCID:
PMC4547212
DOI:
10.1073/pnas.1421372112
[Indexed for MEDLINE]
Free PMC Article

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