bims-cytox1 2022-12-25 papers

Issue of 2022‒12‒25
three papers selected by
Gavin McStay
Liverpool John Moores University

Cells. 2022 Dec 12. pii: 4014. [Epub ahead of print]11(24):

Accelerated Evolution of Cytochrome c in Higher Primates, and Regulation of the Reaction between Cytochrome c and Cytochrome Oxidase by Phosphorylation.

Sue Ellen Brand, Martha Scharlau, Lois Geren, Marissa Hendrix, Clayre Parson, Tyler Elmendorf, Earl Neel, Kaila Pianalto, Jennifer Silva-Nash, Bill Durham, Francis Millett.

Cytochrome c (Cc) underwent accelerated evolution from the stem of the anthropoid primates to humans. Of the 11 amino acid changes that occurred from horse Cc to human Cc, five were at Cc residues near the binding site of the Cc:CcO complex. Single-point mutants of horse and human Cc were made at each of these positions. The Cc:CcO dissociation constant KD of the horse mutants decreased in the order: T89E > native horse Cc > V11I Cc > Q12M > D50A > A83V > native human. The largest effect was observed for the mutants at residue 50, where the horse Cc D50A mutant decreased KD from 28.4 to 11.8 μM, and the human Cc A50D increased KD from 4.7 to 15.7 μM. To investigate the role of Cc phosphorylation in regulating the reaction with CcO, phosphomimetic human Cc mutants were prepared. The Cc T28E, S47E, and Y48E mutants increased the dissociation rate constant kd, decreased the formation rate constant kf, and increased the equilibrium dissociation constant KD of the Cc:CcO complex. These studies indicate that phosphorylation of these residues plays an important role in regulating mitochondrial electron transport and membrane potential ΔΨ.

Keywords: Cytochrome c; Cytochrome c oxidase; electron transfer; phosphorylation

DOI: https://doi.org/10.3390/cells11244014

Biomolecules. 2022 Dec 13. pii: 1863. [Epub ahead of print]12(12):

Mitochondrial Non-Coding RNAs Are Potential Mediators of Mitochondrial Homeostasis.

Weihan Sun, Yijian Lu, Heng Zhang, Jun Zhang, Xinyu Fang, Jianxun Wang, Mengyang Li.

Mitochondria are the energy production center in cells, which regulate aerobic metabolism, calcium balance, gene expression and cell death. Their homeostasis is crucial for cell viability. Although mitochondria own a nucleus-independent and self-replicating genome, most of the proteins, which fulfill mitochondrial functions and mitochondrial quality control, are encoded by the nuclear genome and are imported into mitochondria. Hence, the regulation of mitochondrial protein expression and translocation is considered essential for mitochondrial homeostasis. By means of high-throughput RNA sequencing and bioinformatic analysis, non-coding RNAs localized in mitochondria have been generally identified. They are either generated from the mitochondrial genome or the nuclear genome. The mitochondrial non-coding RNAs can directly interact with mitochondrial DNAs or transcripts to affect gene expression. They can also bind nuclear genome-encoded mitochondrial proteins to regulate their mitochondrial import, protein level and combination. Generally, mitochondrial non-coding RNAs act as regulators for mitochondrial processes including oxidative phosphorylation and metabolism. In this review, we would like to introduce the latest research progressions regarding mitochondrial non-coding RNAs and summarize their identification, biogenesis, translocation, molecular mechanism and function.

Keywords: epigenetics; homeostasis; mitochondria; non-coding RNAs

DOI: https://doi.org/10.3390/biom12121863

Entropy (Basel). 2022 Dec 13. pii: 1813. [Epub ahead of print]24(12):

Contribution of the Collective Excitations to the Coupled Proton and Energy Transport along Mitochondrial Cristae Membrane in Oxidative Phosphorylation System.

Semen V Nesterov, Lev S Yaguzhinsky, Raif G Vasilov, Vasiliy N Kadantsev, Alexey N Goltsov.

The results of many experimental and theoretical works indicate that after transport of protons across the mitochondrial inner membrane (MIM) in the oxidative phosphorylation (OXPHOS) system, they are retained on the membrane-water interface in nonequilibrium state with free energy excess due to low proton surface-to-bulk release. This well-established phenomenon suggests that proton trapping on the membrane interface ensures vectorial lateral transport of protons from proton pumps to ATP synthases (proton acceptors). Despite the key role of the proton transport in bioenergetics, the molecular mechanism of proton transfer in the OXPHOS system is not yet completely established. Here, we developed a dynamics model of long-range transport of energized protons along the MIM accompanied by collective excitation of localized waves propagating on the membrane surface. Our model is based on the new data on the macromolecular organization of the OXPHOS system showing the well-ordered structure of respirasomes and ATP synthases on the cristae membrane folds. We developed a two-component dynamics model of the proton transport considering two coupled subsystems: the ordered hydrogen bond (HB) chain of water molecules and lipid headgroups of MIM. We analytically obtained a two-component soliton solution in this model, which describes the motion of the proton kink, corresponding to successive proton hops in the HB chain, and coherent motion of a compression soliton in the chain of lipid headgroups. The local deformation in a soliton range facilitates proton jumps due to water molecules approaching each other in the HB chain. We suggested that the proton-conducting structures formed along the cristae membrane surface promote direct lateral proton transfer in the OXPHOS system. Collective excitations at the water-membrane interface in a form of two-component soliton ensure the coupled non-dissipative transport of charge carriers and elastic energy of MIM deformation to ATP synthases that may be utilized in ATP synthesis providing maximal efficiency in mitochondrial bioenergetics.

Keywords: collective excitations; mitochondrial cristae membrane; oxidative phosphorylation system; proton conducting networks; proton transport; soliton dynamics

DOI: https://doi.org/10.3390/e24121813