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Evolutionary and functional variation of PGC‐1α in vertebrates
Author(s) -
Le Moine Christophe M.R.,
Genge Christine E.,
Lougheed Stephen E.,
Moyes Christopher D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.757.1
Subject(s) - biology , vertebrate , regulator , phylogenetics , oxidative phosphorylation , microbiology and biotechnology , conserved sequence , mitochondrion , serine , genetics , evolutionary biology , gene , biochemistry , peptide sequence , phosphorylation
In mammals, PGC‐1α is a central regulator of oxidative metabolism through its interactions with NRF‐1 and the PPARs. We examined the role of PGC‐1α in the evolution and development of physiological variations in vertebrates’ oxidative capacity. First, we sought to determine the regulators of the temperature and dietary‐induced metabolic remodeling in goldfish. NRF‐1 and PPARα, respectively, had typical roles in orchestrating mitochondrial proliferation and fatty acid oxidation. In contrast, while goldfish PGC‐1α seemed to be involved in the regulation of the PPAR axis, it did not appear to play a role in NRF‐1 dependent mitochondrial proliferation. To assess the structural basis of these divergent roles in mammals and fish, we investigated the evolutionary trajectory of PGC‐1α in representative vertebrate lineages. The analysis revealed a good conservation of the activation/PPAR interaction domain across vertebrates, whereas the NRF‐1 interaction domain experienced accelerated rates of evolution in Actinopterygians (fish lineages) compared to Sarcopterygians (tetrapod lineages). Furthermore, protein sequence analysis of this variable domain in lineages giving rise to modern teleosts revealed successive serine and glutamine residues insertions with important functional repercussions on PGC‐1α control of mitochondrial proliferation in teleosts. Funded by NSERC (Canada).