bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–08–10
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Isolated cytochrome c oxidase deficiency as a cause of MELAS.
  2. The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.
  1. BMJ Case Rep. 2025 Aug 08. pii: bcr0820080666. [Epub ahead of print]2009
    Isolated cytochrome c oxidase deficiency as a cause of MELAS.
    Walter Rossmanith, Michael Freilinger, Julia Roka, Thomas Raffelsberger, Karin Moser-Their, Daniela Prayer, Günther Bernert, Reginald Bittner.
      Deletion of a single nucleotide (7630delT) within MT-CO2, the gene of subunit II of cytochrome c oxidase (COX), was identified in a clinically typical MELAS case. The deletion-induced frameshift results in a stop codon close to the 5' end of the reading frame. The lack of subunit II (COII) precludes the assembly of COX and leads to the degradation of unassembled subunits, even those not directly affected by the mutation. Despite mitochondrial proliferation and transcriptional upregulation of nuclear and mtDNA-encoded COX genes (including MT-CO2), a severe COX deficiency was found with all investigations of the muscle biopsy (histochemistry, biochemistry, immunoblotting). The 7630delT mutation in MT-CO2 leads to a lack of COII with subsequent misassembly and degradation of respiratory complex IV despite transcriptional upregulation of its subunits. The genetic and pathobiochemical heterogeneity of MELAS appears to be greater than previously appreciated.
    DOI:  https://doi.org/10.1136/bcr.08.2008.0666
  2. FEBS Lett. 2025 Aug 06.
    The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.
    Ulrich Mühlenhoff, Dominik Trauth, Weronika Śliwińska, Linda Boss, Roland Lill.
      Mitochondria contain the bacteria-inherited iron-sulfur cluster assembly (ISC) machinery to generate cellular iron-sulfur (Fe/S) proteins. Mutations in human ISC genes cause severe disorders with a broad clinical spectrum and are associated with strong defects in mitochondrial Fe/S proteins, including respiratory complexes I-III. For unknown reasons, complex IV (aka cytochrome c oxidase), a non-Fe/S, heme-containing enzyme, is severely affected. Using yeast as a model, we show that depletion of Rsm22, the counterpart of the human mitoribosome assembly factor METTL17, phenocopies the defects observed upon impairing late-acting ISC proteins, that is, diminished activities of mitoribosomal translation and respiratory complexes III and IV. Rsm22 binds Fe/S clusters in vivo, thereby satisfactorily explaining the defect of respiratory complex IV in ISC-deficient cells, because this complex contains three mitochondrial DNA-encoded subunits. Impact statement Defects in mitochondrial Fe/S protein biogenesis also impact respiratory complex IV (COX), even though it lacks Fe/S clusters. Here, we show that the mitoribosome assembly factor Rsm22 binds Fe/S clusters in vivo. Rsm22 maturation defects impair mitoribosomal protein translation including COX subunits, explaining the COX defects in Fe/S cluster-deficient cells.
    Keywords:  biogenesis; cytochromes; iron–sulfur protein; mitochondrial DNA; mitochondrial ribosomes; respiratory chain complexes; translation
    DOI:  https://doi.org/10.1002/1873-3468.70129
This page is being maintained by Thomas Krichel. It was last updated on 2025‒08‒11 at 13:52.