bims-resufa 2019-05-12 papers

Issue of 2019–05–12
three papers selected by
Vera Strogolova, Marquette University

Comp Biochem Physiol B Biochem Mol Biol. 2019 May 07. pii: S1096-4959(19)30106-X. [Epub ahead of print]

Hypoxia enhances blood O2 uptake and depresses skeletal muscle O2 consumption in zebrafish (Danio rerio).

Laura Cadiz, Amanda Bundgaard, Hans Malte, Angela Fago.

Zebrafish (Danio rerio) are widely used animal models. Nevertheless, the mechanisms underlying hypoxia tolerance in this species have remained poorly understood. In the present study, we have determined the effects of hypoxia on blood-O2 transport properties and mitochondrial respiration rate in permeabilized muscle fibres of adult zebrafish exposed to either 1) a gradual decrease in O2 levels until fish lost equilibrium (~1 h, acute hypoxia), or 2) severe hypoxia (PO2 ∼ 15 Torr) for 48 h (prolonged hypoxia). Acute, short-term hypoxia caused an increase in hemoglobin (Hb) O2 affinity (decrease in P50), due to a decrease in erythrocyte ATP after erythrocyte swelling. No changes in isoHb expression patterns were observed between hypoxic and normoxic treatments. Prolonged hypoxia elicited additional reponses on O2 consumption: lactate accumulated in the blood, indicating that zebrafish relied on glycolysis for ATP production, and mitochondrial respiration of skeletal muscle was overall significantly inhibited. In addition, male zebrafish had higher hypoxia tolerance (measured as time to loss of equilibrium) than females. The present study contributes to our understanding of the adaptive mechanisms that allow zebrafish, and by inference other fish species, to cope with adverse low O2 levels.

DOI: https://doi.org/10.1016/j.cbpb.2019.05.003

Proc Natl Acad Sci U S A. 2019 May 07. pii: 201903535. [Epub ahead of print]

Extrinsic conditions influence the self-association and structure of IF1, the regulatory protein of mitochondrial ATP synthase.

Vytaute Boreikaite, Basile I M Wicky, Ian N Watt, Jane Clarke, John E Walker.

The endogenous inhibitor of ATP synthase in mitochondria, called IF1, conserves cellular energy when the proton-motive force collapses by inhibiting ATP hydrolysis. Around neutrality, the 84-amino-acid bovine IF1 is thought to self-assemble into active dimers and, under alkaline conditions, into inactive tetramers and higher oligomers. Dimerization is mediated by formation of an antiparallel α-helical coiled-coil involving residues 44-84. The inhibitory region of each monomer from residues 1-46 is largely α-helical in crystals, but disordered in solution. The formation of the inhibited enzyme complex requires the hydrolysis of two ATP molecules, and in the complex the disordered region from residues 8-13 is extended and is followed by an α-helix from residues 14-18 and a longer α-helix from residue 21, which continues unbroken into the coiled-coil region. From residues 21-46, the long α-helix binds to other α-helices in the C-terminal region of predominantly one of the β-subunits in the most closed of the three catalytic interfaces. The definition of the factors that influence the self-association of IF1 is a key to understanding the regulation of its inhibitory properties. Therefore, we investigated the influence of pH and salt-types on the self-association of bovine IF1 and the folding of its unfolded region. We identified the equilibrium between dimers and tetramers as a potential central factor in the in vivo modulation of the inhibitory activity and suggest that the intrinsically disordered region makes its inhibitory potency exquisitely sensitive and responsive to physiological changes that influence the capability of mitochondria to make ATP.

Keywords: ATP hydrolysis; inhibitor; intrinsically disordered protein; mitochondria; regulation

DOI: https://doi.org/10.1073/pnas.1903535116

Chem Commun (Camb). 2019 May 08.

Electric field modulated redox-driven protonation and hydration energetics in energy converting enzymes.

Patricia Saura, Daniel M Frey, Ana P Gamiz-Hernandez, Ville R I Kaila.

Biological energy conversion is catalysed by proton-coupled electron transfer (PCET) reactions that form the chemical basis of respiratory and photosynthetic enzymes. Despite recent advances in structural, biophysical, and computational experiments, the mechanistic principles of these reactions still remain elusive. Based on common functional features observed in redox enzymes, we study here generic mechanistic models for water-mediated long-range PCET reactions. We show how a redox reaction within a buried protein environment creates an electric field that induces hydration changes between the proton acceptor and donor groups, and in turn, lowers the reaction barrier and increases the thermodynamic driving forces for the water-mediated PCET process. We predict linear free energy relationships, and discuss the proposed mechanism in context of PCET in cytochrome c oxidase.

DOI: https://doi.org/10.1039/c9cc01135h