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Mitochondrial Cytochrome c Oxidase Assembly in Health and Human Diseases

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Mitochondrial Disorders Caused by Nuclear Genes

Abstract

Deficiencies in the mitochondrial cytochrome c oxidase (COX) or complex IV, the last enzyme of the mitochondrial respiratory chain, are a frequent cause of mitochondrial diseases in human. Eukaryotic COX is a multimeric copper-heme a, a 3-type oxidase, formed by three catalytic core subunits encoded in the mitochondrial genome and ten nuclear-encoded subunits that act as a protective shield of the core. The biogenesis of the catalytic core subunits, the incorporation of their metal prosthetic groups, and their assembly with imported subunits synthesized in the cytoplasm, involves a growing number of nuclear-encoded ancillary factors. Mutations in the structural subunits and in the assembly factors have been recognized over the last 15 years as important causes of human diseases. In this chapter, we review the current knowledge on human COX biogenesis and discuss the molecular basis of human COX deficiencies due to mutations in proteins involved in the COX assembly process.

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Acknowledgments

Our research is supported by National Institutes of Health Research Grant GM071775A (to A.B.) and a Research Grant (to A.B.) and a Development Grant (to F.F.) from the Muscular Dystrophy Association.

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  1. Department of Neurology, Miller School of Medicine, University of Miami, 1600 NW 10th Ave., RMSB # 2067, 33136, Miami, FL, USA

    Flavia Fontanesi & Antoni Barrientos

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  1. Flavia Fontanesi
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  2. Antoni Barrientos
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Correspondence to Antoni Barrientos .

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  1. , Dept. of Molecular and Human Genetics, Baylor College of Medicine, Baylor Plaza ONE, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

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Fontanesi, F., Barrientos, A. (2013). Mitochondrial Cytochrome c Oxidase Assembly in Health and Human Diseases. In: Wong, LJ. (eds) Mitochondrial Disorders Caused by Nuclear Genes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3722-2_15

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