Journal
MOLECULAR BIOLOGY AND EVOLUTION
Volume 34, Issue 9, Pages 2153-2162Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msx179
Keywords
hypoxia; cytochrome c oxidase; oxygen transport cascade; mitochondria; hypoxia tolerance; fishes
Funding
- Natural Sciences and Engineering Research Council of Canada Discovery grant
- NSERC Canada Graduate Scholarships
Ask authors/readers for more resources
Vertebrate hypoxia tolerance can emerge from modifications to the oxygen (O-2) transport cascade, but whether there is adaptive variation to O-2 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 O-2 binding by mitochondria we undertook a comparative analysis of COX O-2 kinetics across species of intertidal sculpins (Cottidae, Actinopterygii) that vary in hypoxia tolerance. Our analysis revealed a significant relationship between hypoxia tolerance (critical O-2 tension of O-2 consumption rate; P-crit), mitochondrial O-2 binding affinity (O-2 tension at which mitochondrial respiration was half maximal; P-50), and COX O-2-binding affinity (apparent Michaelis-Menten constant for O-2 binding to COX; K-m,K-app O-2). The more hypoxia tolerant species had both a lower mitochondrial P-50 and lower COX K-m,K-app O-2, facilitating the maintenance of mitochondrial function to a lower O-2 tension than in hypoxia intolerant species. Additionally, hypoxia tolerant species had a lower overall COX V-max 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 O-2 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 K-m,K-app O-2. 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 K-m,K-app O-2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available