According to the endosymbiotic theory, mitochondria originate from a free-living alpha-proteobacteria that established an intracellular symbiosis with the ancestor of present-day eukaryotic cells. During the bacterium-to-organelle transformation, the proto-mitochondrial proteome has undergone a massive turnover, whereby less than 20 % of modern mitochondrial proteomes can be traced back to the bacterial ancestor. Moreover, mitochondrial proteomes from several eukaryotic organisms, for example, yeast and human, show a rather modest overlap, reflecting differences in mitochondrial physiology. Those differences may result from the combination of differential gain and loss of genes and retargeting processes among lineages. Therefore, an evolutionary signature, also called “phylogenetic profile”, could be generated for every mitochondrial protein. Here, we present two evolutionary biology approaches to study mitochondrial physiology: the first strategy, which we refer to as “comparative physiology,” allows the de novo identification of mitochondrial proteins involved in a physiological function; the second, known as “phylogenetic profiling,” allows to predict protein functions and functional interactions by comparing phylogenetic profiles of uncharacterized and known components.
Gabaldón T, Huynen MA (2007) From endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism. PLoS Comput Biol 3:e219PubMedCentralPubMedCrossRefGoogle Scholar
Gabaldón T, Huynen MA (2005) Lineage-specific gene loss following mitochondrial endosymbiosis and its potential for function prediction in eukaryotes. Bioinformatics 21:144–150CrossRefGoogle Scholar
Huynen MA, Snel B, Bork P et al (2001) The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum Mol Genet 10:2463–2468PubMedCrossRefGoogle Scholar
Gabaldón T, Rainey D, Huynen MA (2005) Tracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I). J Mol Biol 348:857–870PubMedCrossRefGoogle Scholar
Franceschini A, Szklarczyk D, Frankild S et al (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41:D808–D815PubMedCentralPubMedCrossRefGoogle Scholar
Plovanich M, Bogorad RL, Sancak Y et al (2013) MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One 8:e55785PubMedCentralPubMedCrossRefGoogle Scholar
Raffaello A, De Stefani D, Sabbadin D et al (2013) The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J 32:2362–2376PubMedCentralPubMedCrossRefGoogle Scholar