MT-CO2 – Leigh Syndrome

Cytochrome c oxidase subunit II (MT-CO2) is encoded by mitochondrial DNA and forms the catalytic core of Complex IV, essential for electron transport and ATP synthesis. In a single reported case, a 2-year-5-month‐old child presented with classical Leigh syndrome features, and muscle biopsy demonstrated markedly reduced CCO and cytochrome a+a3 activities, moderate NADH–cytochrome c reductase deficiency, and selective loss of CCO subunits 1 and 4 in multiple tissues, while other respiratory complexes were preserved (PMID:2159985). Genetic analysis excluded large-scale mtDNA deletions, suggesting an unresolved COX2 defect.

No specific MT-CO2 coding variant has been definitively linked to Leigh syndrome, and segregation or additional familial cases are lacking, limiting clinical genetic evidence. Functional studies using Saccharomyces cerevisiae models have delineated critical elements in the COX2 mRNA 5′-untranslated leader required for translational activation by Pet111p, with deletion of bases -30 to -2 completely abolishing COX2 translation and respiratory competence (PMID:8167413). These findings underscore the importance of proper COX2 expression for Complex IV assembly but have not yet been correlated to human Leigh syndrome pathogenesis.

References

• Journal of the neurological sciences • 1990 • Progressive cytochrome c oxidase deficiency in a case of Leigh’s encephalomyelopathy. PMID:2159985
• Molecular biology of the cell • 1993 • Alteration of the Saccharomyces cerevisiae COX2 mRNA 5'-untranslated leader by mitochondrial gene replacement and functional interaction with the translational activator protein PET111. PMID:8167413

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