bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2023‒11‒26
six papers selected by
Gavin McStay, Liverpool John Moores University
  1. Carnation Italian Ringspot Virus p36 Expression Induces Mitochondrial Fission and Respiratory Chain Complex Impairment in Yeast.
  2. Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics.
  3. Oxidation of Arabidopsis thaliana COX19 Using the Combined Action of ERV1 and Glutathione.
  4. Mechanisms of stress management in mitochondrial protein import.
  5. Heme Biosynthesis is Crucial for Cell Survival and Mitochondrial OXPHOS after X Irradiation.
  6. Profiling cardiomyocytes at single cell resolution reveals COX7B could be a potential target for attenuating heart failure in cardiac hypertrophy.
  1. Int J Mol Sci. 2023 Nov 10. pii: 16166. [Epub ahead of print]24(22):
    Carnation Italian Ringspot Virus p36 Expression Induces Mitochondrial Fission and Respiratory Chain Complex Impairment in Yeast.
    Giuseppe Petrosillo, Angelo De Stradis, Domenico Marzulli, Luisa Rubino, Sergio Giannattasio.
      Positive-strand RNA virus replication invariably occurs in association with host cell membranes, which are induced to proliferate and rearrange to form vesicular structures where the virus replication complex is assembled. In particular, carnation Italian ringspot virus (CIRV) replication takes place on the mitochondrial outer membrane in plant and yeast cells. In this work, the model host Saccharomyces cerevisiae was used to investigate the effects of CIRV p36 expression on the mitochondrial structure and function through the determination of mitochondrial morphology, mitochondrial respiratory parameters, and respiratory chain complex activities in p36-expressing cells. CIRV p36 ectopic expression was shown to induce alterations in the mitochondrial network associated with a decrease in mitochondrial respiration and the activities of NADH-cyt c, succinate-cyt c (C II-III), and cytochrome c oxidase (C IV) complexes. Our results suggest that the decrease in respiratory complex activity could be due, at least in part, to alterations in mitochondrial dynamics. This yeast-based model will be a valuable tool for identifying molecular targets to develop new anti-viral strategies.
    Keywords:  (+)RNA virus; CIRV; mitochondria; p36; respiratory complex; yeast
    DOI:  https://doi.org/10.3390/ijms242216166
  2. Brain Sci. 2023 Oct 31. pii: 1534. [Epub ahead of print]13(11):
    Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics.
    Virginia Haynes, Cecilia Giulivi.
      Targeted nitric oxide production is relevant for maintaining cellular energy production, protecting against oxidative stress, regulating cell death, and promoting neuroprotection. This study aimed to characterize the putative interaction of nitric-oxide synthase with mitochondrial proteins. The primary finding of this study is that cytochrome c oxidase (CCO) subunit IV (CCOIV) is associated directly with NOS in brain mitochondria when calcium ions are present. The matrix side of CCOIV binds to the N-terminus of NOS, supported by the abrogation of the binding by antibodies towards the N-terminus of NOS. Evidence supporting the interaction between CCOIV and NOS was provided by the coimmunoprecipitation of NOS from detergent-solubilized whole rat brain mitochondria with antibodies to CCOIV and the coimmunoprecipitation of CCOIV from crude brain NOS preparations using antibodies to NOS. The CCOIV domain that interacts with NOS was identified using a series of overlapping peptides derived from the primary sequence of CCOIV. As calcium ions not only activate NOS, but also facilitate the docking of NOS to CCOIV, this study points to a dynamic mechanism of controlling the bioenergetics by calcium changes, thereby adapting bioenergetics to cellular demands.
    Keywords:  Complex IV; bioenergetics; mitochondria; nitric oxide; nitric oxide synthase; oxygen; protein–protein interaction
    DOI:  https://doi.org/10.3390/brainsci13111534
  3. Antioxidants (Basel). 2023 Nov 01. pii: 1949. [Epub ahead of print]12(11):
    Oxidation of Arabidopsis thaliana COX19 Using the Combined Action of ERV1 and Glutathione.
    Flavien Zannini, Johannes M Herrmann, Jérémy Couturier, Nicolas Rouhier.
      Protein import and oxidative folding within the intermembrane space (IMS) of mitochondria relies on the MIA40-ERV1 couple. The MIA40 oxidoreductase usually performs substrate recognition and oxidation and is then regenerated by the FAD-dependent oxidase ERV1. In most eukaryotes, both proteins are essential; however, MIA40 is dispensable in Arabidopsis thaliana. Previous complementation experiments have studied yeast mia40 mutants expressing a redox inactive, but import-competent versions of yeast Mia40 using A. thaliana ERV1 (AtERV1) suggest that AtERV1 catalyzes the oxidation of MIA40 substrates. We assessed the ability of both yeast and Arabidopsis MIA40 and ERV1 recombinant proteins to oxidize the apo-cytochrome reductase CCMH and the cytochrome c oxidase assembly protein COX19, a typical MIA40 substrate, in the presence or absence of glutathione, using in vitro cysteine alkylation and cytochrome c reduction assays. The presence of glutathione used at a physiological concentration and redox potential was sufficient to support the oxidation of COX19 by AtERV1, providing a likely explanation for why MIA40 is not essential for the import and oxidative folding of IMS-located proteins in Arabidopsis. The results point to fundamental biochemical differences between Arabidopsis and yeast ERV1 in catalyzing protein oxidation.
    Keywords:  ERV1; MIA40; glutathione; mitochondrial intermembrane space; oxidative folding
    DOI:  https://doi.org/10.3390/antiox12111949
  4. Biochem Soc Trans. 2023 Nov 21. pii: BST20230377. [Epub ahead of print]
    Mechanisms of stress management in mitochondrial protein import.
    Maryam Mukhtar, Krutika Thakkur, Agnieszka Chacinska, Piotr Bragoszewski.
      Mitochondria are vital to the functions of eukaryotic cells. Most mitochondrial proteins are transported into the organelle following their synthesis by cytoplasmic ribosomes. However, precise protein targeting is complex because the two diverse lipid membranes encase mitochondria. Efficient protein translocation across membranes and accurate sorting to specific sub-compartments require the cooperation of multiple factors. Any failure in mitochondrial protein import can disrupt organelle fitness. Proteins intended for mitochondria make up a significant portion of all proteins produced in the cytosol. Therefore, import defects causing their mislocalization can significantly stress cellular protein homeostasis. Recognition of this phenomenon has increased interest in molecular mechanisms that respond to import-related stress and restore proteostasis, which is the focus of this review. Significantly, disruptions in protein homeostasis link strongly to the pathology of several degenerative disorders highly relevant in ageing societies. A comprehensive understanding of protein import quality control will allow harnessing this machinery in therapeutic approaches.
    Keywords:  mitochondria; protein degradation; protein transport; proteostasis; proteotoxicity; stress
    DOI:  https://doi.org/10.1042/BST20230377
  5. Radiat Res. 2023 Nov 21.
    Heme Biosynthesis is Crucial for Cell Survival and Mitochondrial OXPHOS after X Irradiation.
    Tomoki Bo, Koen Van Wijk, Osamu Nakajima.
      Heme is an essential component of the hemoproteins involved in the mitochondrial electron transport chain (ETC). Cancer cells have been reported to display high heme levels and increased activity of heme-containing proteins. Consistently, inhibition of heme biosynthesis by the ALAD inhibitor succinylacetone (SA) has been shown to reduce tumor cell survival. These observations indicate that heme biosynthesis is essential for cancer cell proliferation. X irradiation has been shown to increase mitochondrial mass, membrane potential, oxygen consumption, reactive oxygen species (ROS) production, and ATP synthesis. This finding suggests that radiation activates mitochondrial oxidative phosphorylation (OXPHOS). However, although heme is an essential component of the mitochondrial ETC, whether radiation influences heme biosynthesis remains unclear. In this study, we evaluated heme biosynthesis activity after X irradiation and examined the effects of heme biosynthesis inhibition by SA on cellular radiosensitivity and mitochondrial OXPHOS function. We demonstrated that X irradiation significantly increased ALAS1 mRNA levels and cellular heme content. Inhibition of heme biosynthesis by SA significantly decreased cellular heme content and sensitized cancer cells to radiation. We also showed that SA reduced cellular ATP levels, mitochondrial membrane potential, and mitochondrial ROS production, suggesting mitochondrial OXPHOS dysfunction. SA decreased the expression of mitochondrial heme-related proteins COX2 and cytochrome c but did not influence COX1 and VDAC expression. These results indicate that inhibition of heme biosynthesis decreased mitochondrial ETC protein expression and OXPHOS activity, which triggered cellular ATP depletion and radiosensitization after X irradiation. In summary, heme biosynthesis is upregulated by X irradiation and is essential for mitochondrial OXPHOS and cell survival.
    DOI:  https://doi.org/10.1667/RADE-23-00035.1
  6. J Mol Cell Cardiol. 2023 Nov 16. pii: S0022-2828(23)00187-6. [Epub ahead of print]186 45-56
    Profiling cardiomyocytes at single cell resolution reveals COX7B could be a potential target for attenuating heart failure in cardiac hypertrophy.
    Shi Chen, Kui Wang, Jingyu Wang, Xiao Chen, Menghao Tao, Dan Shan, Xiumeng Hua, Shengshou Hu, Jiangping Song.
      Cardiac hypertrophy can develop to end-stage heart failure (HF), which inevitably leading to heart transplantation or death. Preserving cardiac function in cardiomyocytes (CMs) is essential for improving prognosis in hypertrophic cardiomyopathy (HCM) patients. Therefore, understanding transcriptomic heterogeneity of CMs in HCM would be indispensable to aid potential therapeutic targets investigation. We isolated primary CM from HCM patients who had extended septal myectomy, and obtained transcriptomes in 338 human primary CM with single-cell tagged reverse transcription (STRT-seq) approach. Our results revealed that CMs could be categorized into three subsets in nonfailing HCM heart: high energy synthesis cluster, high cellular metabolism cluster and intermediate cluster. The expression of electron transport chain (ETC) was up-regulated in larger-sized CMs from high energy synthesis cluster. Of note, we found the expression of Cytochrome c oxidase subunit 7B (COX7B), a subunit of Complex IV in ETC had trends of positively correlation with CMs size. Further, by assessing COX7B expression in HCM patients, we speculated that COX7B was compensatory up-regulated at early-stage but down-regulated in failing HCM heart. To test the hypothesis that COX7B might participate both in hypertrophy and HF progression, we used adeno associated virus 9 (AAV9) to mediate the expression of Cox7b in pressure overload-induced mice. Mice in vivo data supported that knockdown of Cox7b would accelerate HF and Cox7b overexpression could restore partial cardiac function in hypertrophy. Our result highlights targeting COX7B and preserving energy synthesis in hypertrophic CMs could be a promising translational direction for HF therapeutic strategy.
    Keywords:  AAV9; Cardiomyocyte; Cytochrome c oxidase subunit 7B; Hypertrophy; Single-cell sequencing
    DOI:  https://doi.org/10.1016/j.yjmcc.2023.11.005
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