Lau 2017 Mol Biol Evol
| Lau GY, Mandic M, Richards JG (2017) Evolution of cytochrome c oxidase in hypoxia tolerant Sculpins (Cottidae, Actinopterygii). Mol Biol Evol 34:2153-62. |
Lau GY, Mandic M, Richards JG (2017) Mol Biol Evol
Abstract: Vertebrate hypoxia tolerance can emerge from modifications to the oxygen (O2) transport cascade, but whether there is adaptive variation to O2 binding at the terminus of this cascade, mitochondrial cytochrome c oxidase (COX), is not known. In order to address the hypothesis that hypoxia tolerance is associated with enhanced O2 binding by mitochondria we undertook a comparative analysis of COX O2 kinetics across species of intertidal sculpins (Cottidae, Actinopterygii) that vary in hypoxia tolerance. Our analysis revealed a significant relationship between hypoxia tolerance (critical O2 tension of O2 consumption rate; Pcrit), mitochondrial O2 binding affinity (O2 tension at which mitochondrial respiration was half maximal; P50), and COX O2-binding affinity (apparent Michaelis-Menten constant for O2 binding to COX; Km,app O2). The more hypoxia tolerant species had both a lower mitochondrial P50 and lower COX Km,app O2, facilitating the maintenance of mitochondrial function to a lower O2 tension than in hypoxia intolerant species. Additionally, hypoxia tolerant species had a lower overall COX Vmax but higher mitochondrial COX respiration rate when expressed relative to maximal electron transport system respiration rate. In silico analyses of the COX3 subunit postulated as the entry point for O2 into the COX protein catalytic core, points to variation in COX3 protein stability (estimated as free energy of unfolding) contributing to the variation in COX Km,app O2. We propose that interactions between COX3 and cardiolipin at four amino acid positions along the same alpha-helix forming the COX3 v-cleft represent likely determinants of interspecific differences in COX Km,app O2.
© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: [email protected]. • Keywords: Cytochrome c oxidase, Fishes, Hypoxia, Hypoxia tolerance, Mitochondria, Oxygen transport cascade • Bioblast editor: Kandolf G • O2k-Network Lab: CA Vancouver Richards JG
Labels: MiParea: Respiration, Comparative MiP;environmental MiP
Stress:Hypoxia Organism: Fishes Tissue;cell: Nervous system Preparation: Isolated mitochondria
Regulation: Oxygen kinetics Coupling state: LEAK, OXPHOS, ET Pathway: CIV, NS, ROX HRR: Oxygraph-2k, TPP
2017-10
