bims-resufa 2020-08-23 papers

Issue of 2020‒08‒23
three papers selected by
Vera Strogolova
Strong Microbials, Inc

Commun Biol. 2020 Aug 18. 3(1): 451

Thermodynamic efficiency, reversibility, and degree of coupling in energy conservation by the mitochondrial respiratory chain.

Mårten Wikström, Roger Springett.

The protonmotive mitochondrial respiratory chain, comprising complexes I, III and IV, transduces free energy of the electron transfer reactions to an electrochemical proton gradient across the inner mitochondrial membrane. This gradient is used to drive synthesis of ATP and ion and metabolite transport. The efficiency of energy conversion is of interest from a physiological point of view, since the energy transduction mechanisms differ fundamentally between the three complexes. Here, we have chosen actively phosphorylating mitochondria as the focus of analysis. For all three complexes we find that the thermodynamic efficiency is about 80-90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis. However, when net ATP synthesis stops at a high ATP/ADP.Pi ratio, and mitochondria reach "State 4" with an elevated proton gradient, the degree of coupling drops substantially. The mechanistic cause and the physiological implications of this effect are discussed.

DOI: https://doi.org/10.1038/s42003-020-01192-w

Inorg Chem. 2020 Aug 17. 59(16): 11542-11553

Role of the Two Metals in the Active Sites of Heme Copper Oxidases-A Study of NO Reduction in cbb3 Cytochrome c Oxidase.

Margareta R A Blomberg.

The superfamily of heme copper oxidases reduces molecular oxygen or nitric oxide, and the active sites comprise a high-spin heme group (a3 or b3) and a non-heme metal (CuB or FeB). The cbb3 C family of cytochrome c oxidases, with the high-spin heme b3 and CuB in the active site, is a subfamily of the heme copper oxidases that can reduce both molecular oxygen, which is the main substrate, and nitric oxide. The mechanism for NO reduction in cbb3 oxidase is studied here using hybrid density functional theory and compared to other cytochrome c oxidases (A and B families), with a high-spin heme a3 and CuB in the active site, and to cytochrome c dependent NO reductase, with a high-spin heme b3 and a non-heme FeB in the active site. It is found that the reaction mechanism and the detailed reaction energetics of the cbb3 oxidases are not similar to those of cytochrome c dependent NO reductase, which has the same type of high-spin heme group but a different non-heme metal. This is in contrast to earlier expectations. Instead, the NO reduction mechanism in cbb3 oxidases is very similar to that in the other cytochrome c oxidases, with the same non-heme metal, CuB, and is independent of the type of high-spin heme group. The conclusion is that the type of non-heme metal (CuB or FeB) in the active site of the heme copper oxidases is more important for the reaction mechanisms than the type of high-spin heme, at least for the NO reduction reaction. The reason is that the proton-coupled reduction potentials of the active site cofactors determine the energetics for the NO reduction reaction, and they depend to a larger extent on the non-heme metal. Observed differences in NO reduction reactivity among the various cytochrome c oxidases may be explained by differences outside the BNC, affecting the rate of proton transfer, rather than in the BNC itself.

DOI: https://doi.org/10.1021/acs.inorgchem.0c01351

Comp Biochem Physiol A Mol Integr Physiol. 2020 Aug 14. pii: S1095-6433(20)30144-6. [Epub ahead of print] 110792

Nitric oxide homeostasis is maintained during acute in vitro hypoxia and following reoxygenation in naked mole-rat but not mouse cortical neurons.

H Wang Tina, Eaton Liam, E Pamenter Matthew.

Reactive nitrogen species (RNS), including nitric oxide (NO), are important cellular messengers when tightly regulated, but unregulated production of RNS during hypoxia or ischemia and reoxygenation is deleterious to hypoxia-intolerant brain. Therefore, maintaining NO homeostasis during hypoxia/ischemia and reoxygenation may be a hallmark of hypoxia-tolerant brain. Unlike most mammals, naked mole-rats (NMRs; Heterocephalus glaber) are tolerant of repeated bouts of hypoxia in vivo. Although there is some evidence that NMR brain is tolerant of hypoxia/ischemia, little is known about the underlying neuroprotective mechanism(s), and their tolerance to reoxygenation injury has not been examined. We hypothesized that NMR brain would maintain NO homeostasis better than hypoxia-intolerant mouse brain during hypoxic/ischemic stresses and following reoxygenation. To test this, we exposed adult NMR and mouse cortical slices to transitions from normoxia (21% O2) to hypoxia (< 1% O2) or ischemia (oxygen glucose deprivation, OGD), followed by reoxygenation, while measuring neuronal NO production. We report that NMR cortical neurons maintains NO homeostasis during hypoxia/OGD and avoid bursts of NO upon reoxygenation. Conversely, mouse cortical neurons maintain NO homeostasis in OGD but not hypoxia and exhibit a burst of NO upon reperfusion. This suggests that maintenance of NO homeostasis during fluctuating O2 availability may be a contributing neuroprotective mechanism against hypoxia/ischemia and reoxygenation injury in hypoxia-tolerant NMR brain.

Keywords: Free radicals; Ischemia; Oxygen glucose deprivation; Reactive nitrogen species; Reperfusion

DOI: https://doi.org/10.1016/j.cbpa.2020.110792