bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–01–12
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. COA5 has an essential role in the early stage of mitochondrial complex IV assembly.
  2. Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease.
  1. Life Sci Alliance. 2025 Mar;pii: e202403013. [Epub ahead of print]8(3):
    COA5 has an essential role in the early stage of mitochondrial complex IV assembly.
    Jia Xin Tang, Alfredo Cabrera-Orefice, Jana Meisterknecht, Lucie S Taylor, Geoffray Monteuuis, Maria Ekman Stensland, Adam Szczepanek, Karen Stals, James Davison, Langping He, Sila Hopton, Tuula A Nyman, Christopher B Jackson, Angela Pyle, Monika Winter, Ilka Wittig, Robert W Taylor.
      Pathogenic variants in cytochrome c oxidase assembly factor 5 (COA5), a proposed complex IV (CIV) assembly factor, have been shown to cause clinical mitochondrial disease with two siblings affected by neonatal hypertrophic cardiomyopathy manifesting a rare, homozygous COA5 missense variant (NM_001008215.3: c.157G>C, p.Ala53Pro). The most striking observation in the affected individuals was an isolated impairment in the early stage of mitochondrial CIV assembly. In this study, we report an unrelated family in whom we have identified the same COA5 variant with patient-derived fibroblasts and skeletal muscle biopsies replicating an isolated CIV deficiency. A CRISPR/Cas9-edited homozygous COA5 knockout U2OS cell line with a similar biochemical profile was generated to interrogate the functional role of the human COA5 protein. Mitochondrial complexome profiling pinpointed a role of COA5 in early CIV assembly, more specifically, its involvement in the stage between MTCO1 maturation and the incorporation of MTCO2. We therefore propose that the COA5 protein plays an essential role in the biogenesis of MTCO2 and its integration into the early CIV assembly intermediate for downstream assembly of the functional holocomplex.
    DOI:  https://doi.org/10.26508/lsa.202403013
  2. Commun Biol. 2025 Jan 09. 8(1): 24
    Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease.
    Julie Faitg, Tracey Davey, Ross Laws, Conor Lawless, Helen Tuppen, Eric Fitton, Doug Turnbull, Amy E Vincent.
      Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondrial morphology evaluation at high magnification, even fewer that do so in situ and none in human muscle biopsies. Therefore, we have developed a method which combines functional assessment of mitochondria through Cytochrome c Oxidase (COX) histochemistry, with a 3D electron microscopy (EM) technique, serial block-face scanning electron microscopy (SBFSEM). Here we apply COX-SBFSEM to muscle samples from patients with single, large-scale mtDNA deletions, a cause of mitochondrial disease. These deletions cause oxidative phosphorylation deficiency, which can be observed through changes in COX activity. One of the main advantages of combining 3D-EM with the COX reaction is the ability to look at how per-mitochondrion oxidative phosphorylation status is spatially distributed within muscle fibres. Here we show a robust spatial pattern in COX-positive and intermediate-fibres and that the spatial pattern is less clear in COX-deficient fibres.
    DOI:  https://doi.org/10.1038/s42003-024-07389-7
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