title: Stability of mitochondrial membrane proteins in terrestrial vertebrates predicts aerobic capacity and longevity.
abstract: The cellular energy produced by mitochondria is a fundamental currency of life. However, the extent to which mitochondrial (mt) performance (power and endurance) is adapted to habitats and life strategies of vertebrates is not well understood. A global analysis of mt genomes revealed that hydrophobicity (HYD) of mt membrane proteins (MMPs) is much lower in terrestrial vertebrates than in fishes and shows a strong negative correlation with serine/threonine composition (STC). Here, we present evidence that this systematic feature of MMPs was crucial for the evolution of large terrestrial vertebrates with high aerobic capacity. An Arrhenius-type equation gave positive correlations between STC and maximum life span (MLS) in terrestrial vertebrates (with a few exceptions relating to the lifestyle of small animals with a high resting metabolic rate [RMR]) and negative correlations in secondary marine vertebrates, such as cetaceans and alligators (which returned from land to water, utilizing buoyancy with increased body size). In particular, marked STC increases in primates (especially hominoids) among placentals were associated with very high MLS values. We connected these STC increases in MMPs with greater stability of respiratory complexes by estimating the degradation of the Arrhenius plot given by accelerating mtRMR up to mt maximum metabolic rate. Both mtRMR and HYD in terrestrial vertebrates decreased with increasing body mass. Decreases in mtRMR raise MMP stability when high mobility is not required, whereas decreased HYD may weaken this stability under the hydrophobic environment of lipid bilayer. High maximal metabolic rates (5-10 RMR), which we postulate require high MMP mobility, presumably render MMPs more unstable. A marked rise in STC may therefore be essential to stabilize MMPs, perhaps as dynamic supercomplexes, via hydrogen bonds associated with serine/threonine motifs.
authors.affiliation: Center of Medical Information Science, Kochi Medical School, Nankoku, Kochi, Japan. kitazoeyasuhiro@yahoo.co.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kitazoe
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kishino
authors.forename: Masami
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsui
authors.forename: Nick
authors.initials: N
authors.lastname: Lane
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D019069:Cell Respiration; D006801:Humans; D006860:Hydrogen Bonding; D008136:Longevity; D008565:Membrane Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014714:Vertebrates
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D013912:Threonine; D012694:Serine