bims-cytox1 2024-10-06 papers

Issue of 2024‒10‒06
two papers selected by
Gavin McStay, Liverpool John Moores University

Commun Biol. 2024 Sep 28. 7(1): 1214

Evolution of a biological thermocouple by adaptation of cytochrome c oxidase in a subterrestrial metazoan, Halicephalobus mephisto.

Megan N Guerin, TreVaughn S Ellis, Mark J Ware, Alexandra Manning, Ariana A Coley, Ali Amini, Adaeze G Igboanugo, Amaya P Rothrock, George Chung, Kristin C Gunsalus, John R Bracht.

In this study, we report a biological temperature-sensing electrical regulator in the cytochrome c oxidase of the Devil Worm, Halicephalobus mephisto. This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change. We obtained the complete mitochondrial genome sequence of this organism and show through dN/dS analysis evidence of positive selection in H. mephisto cytochrome c oxidase subunits. Seventeen of these positively selected amino acid substitutions were located in proximity to the H- and K-pathway proton channels of the complex. Surprisingly, the H. mephisto cytochrome c oxidase completely shuts down at low temperatures (20 °C), leading to a 4.8-fold reduction in the transmembrane proton gradient (ΔΨm) compared to optimal temperature (37 °C). Direct measurement of oxygen consumption found a corresponding 4.6-fold drop at 20 °C compared to 37 °C. Correspondingly, the lifecycle of H. mephisto takes four times longer at low temperature than at higher. This elegant evolutionary adaptation creates a finely-tuned mitochondrial temperature sensor, allowing this ectothermic organism to maximize its reproductive success across varying environmental temperatures.

DOI: https://doi.org/10.1038/s42003-024-06886-z

Talanta. 2024 Sep 24. pii: S0039-9140(24)01324-9. [Epub ahead of print]282 126945

Engineering Cu-Ce-a nanozymes: Revolutionary alloy nanomaterials mimicking cytochrome c oxidase for ultra-sensitive cytochrome c detection.

Huan Yang, Jingjie Du, Wenzhu Wang, Ting Li, Ronghao Zhang, Yan Yu, Kai Li, Yuqing Lin.

The design of synthetic analogs of cytochrome c oxidase (CcO) is a formidable task due to its intricate structure encompassing multiple metal prosthetic sites and protein subunits. In recent years, artificial enzymes based on alloy nanomaterials have garnered significant attention due to the alloy design approach holds promise for the effective tuning of the properties of metal catalysts. In this study, we present copper-cerium alloy nanozymes (Cu-Ce-a NEs), where Cu mimics the active site of CcO, while Ce endows the alloy phase and enhances the capacity to catalyze the oxidation to cytochrome c (Cyt c). Cu-Ce-a NEs functionally mimics CcO, the terminal enzyme in the respiratory electron transport chain (ETC), by catalyzing the four-electron reduction of dioxygen to water. Utilizing the CcO-like properties of Cu-Ce-a NEs, we successfully implemented the electrochemical detection of Cyt c. The Cu-Ce-a NEs based electrochemical sensor revealed a favorable linear range spanning from 2 to 20 μM Cyt c, with a detection limit (LOD) of 2 μM. This method demonstrates high accuracy in Cyt c quantitation in pharmaceuticals, with results closely aligning with the actual concentrations. This finding not only offers new perspectives in the design of enzyme analogs, but also underscores the potential of this method for clinical Cyt c detection, highlighting its significance in biomedical research and diagnostics.

Keywords: Alloy; CcO; Cu–Ce-a NEs; Cyt c; Electrochemical sensor

DOI: https://doi.org/10.1016/j.talanta.2024.126945