Mutations in the Yeast Cox12 Subunit Severely Compromise the Activity of the Mitochondrial Complex IV.

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  • Additional Information
    • Source:
      Publisher: MAIK Nauka/Interperiodica Country of Publication: United States NLM ID: 0376536 Publication Model: Print Cited Medium: Internet ISSN: 1608-3040 (Electronic) Linking ISSN: 00062979 NLM ISO Abbreviation: Biochemistry (Mosc) Subsets: MEDLINE
    • Publication Information:
      Publication: <2007->: Moscow : MAIK Nauka/Interperiodica
      Original Publication: New York, Consultants Bureau [etc.]
    • Subject Terms:
      Mutation, Missense*; Electron Transport Complex IV/*metabolism ; Membrane Proteins/*metabolism ; Protein Subunits/*metabolism ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae Proteins/*metabolism; Amino Acid Substitution ; Electron Transport Complex IV/genetics ; Humans ; Membrane Proteins/genetics ; Protein Subunits/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics
    • Abstract:
      Cytochrome c oxidase 6B1 (COX6B1) is one of the less characterized subunits of the mitochondrial electron transport chain complex IV (CIV). Here, we studied the pathobiochemical and respiratory functions of Cox12 (yeast ortholog of COX6B1) using Saccharomyces cerevisiae BY4741 (cox12Δ) cells deficient by the Cox12 protein. The cells exhibited severe growth deficiency in the respiratory glycerol-ethanol medium, which could be reverted by complementation with the yeast COX12 or human COX6B1 genes. Cox12 with arginine 17 residue substituted by histidine (R17H) or cysteine (R17C) (mutations analogous to those observed in human patients) failed to complement the loss of Cox12 function. When cox12Δ cells were grown in rich respiratory/fermentative galactose medium, no changes in the expression of individual respiratory chain subunits were observed. Blue native PAGE/Western blotting analysis using antibodies against Rip1 and Cox1, which are specific components of complexes III (CIII) and IV (CIV), respectively, revealed no noticeable decrease in the native CIII 2 CIV 2 and CIII 2 CIV 1 supercomplexes (SCs). However, the association of the respiratory SC factor 2 (Rcf2) and Cox2 subunit within the SCs of cox12Δ cells was reduced, while the specific activity of CIV was downregulated by 90%. Both basal respiration and succinate-ADP stimulated state 3 respiration, as well as the mitochondrial membrane potential, were decreased in cox12Δ cells. Furthermore, cox12Δ cells and cells synthesizing Cox12 mutants R17H and R17C showed higher sensitivity to the H2O2-induced oxidative stress compared to the wild-type (WT) cells. In silico structural modeling of the WT yeast SCs revealed that Cox12 forms a network of interactions with Rcf2 and Cox2. Together, our results establish that Cox12 is essential for the CIV activity.
    • Contributed Indexing:
      Keywords: Cox12; complex IV; cytochrome c oxidase 6B1; supercomplexes
    • Accession Number:
      0 (Membrane Proteins)
      0 (Protein Subunits)
      0 (Saccharomyces cerevisiae Proteins)
      EC 1.9.3.1 (Electron Transport Complex IV)
    • Publication Date:
      Date Created: 20211223 Date Completed: 20220124 Latest Revision: 20220124
    • Publication Date:
      20221213
    • Accession Number:
      10.1134/S0006297921120105
    • Accession Number:
      34937540