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The Many Clinical Faces of Cytochrome c Oxidase Deficiency

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Book cover Mitochondrial Oxidative Phosphorylation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 748))

Abstract

Cytochrome c oxidase (COX) catalyzes the last step in respiration, transferring electrons from cytochrome c to molecular oxygen and coupling electron transfer with proton translocation from the mitochondrial matrix to the intermembrane space. COX is composed of 13 subunits, three larger catalytic subunits encoded by mitochondrial DNA (mtDNA) and ten subunits encoded by nuclear DNA. Clinically heterogeneous human diseases were attributed to COX deficiency since the 1970s, mostly based on histochemical or biochemical data in muscle biopsies. Here, we revisit the COX deficiencies described before the molecular era, assess the value of COX histochemistry in conjunction with succinate dehydrogenase (SDH) stain, and review the clinical presentations of primary COX deficiencies defined at the molecular level. In general, mutations in mtDNA COX genes are associated with milder and later onset clinical syndromes, probably due to heteroplasmy. Mutations affecting nuclear-encoded COX subunits (“direct hits”) are extremely rare whereas mutations affecting assembly proteins (“indirect hits”) account for most COX deficiencies and the list keeps growing. Onset is generally in infancy and survival into adolescence or adult life is infrequent. The most common neurological disorder is Leigh syndrome, either alone or associated with cardiopathy, hepatopathy, or nephropathy.

This chapter is dedicated to the memory of Eduardo Bonilla (1936–2010).

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Acknowledgments

This work has been supported by NICHD grant P01-H23062 and by the Marriott Mitochondrial Disorder Clinical Research Fund (MMDCRF).

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Authors and Affiliations

  1. Department of Neurology, Columbia University Medical Center, College of Physicians & Surgeons, New York, NY, 10032, USA

    Salvatore DiMauro

  2. Department of Neurology, and Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

    Kurenai Tanji

  3. Department of Neurology , and Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA

    Eric A. Schon

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  1. Salvatore DiMauro
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  2. Kurenai Tanji
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  3. Eric A. Schon
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Correspondence to Salvatore DiMauro .

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  1. Philipps-Universitaet Marburg, Marburg, 35032, Germany

    Bernhard Kadenbach

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DiMauro, S., Tanji, K., Schon, E.A. (2012). The Many Clinical Faces of Cytochrome c Oxidase Deficiency. In: Kadenbach, B. (eds) Mitochondrial Oxidative Phosphorylation. Advances in Experimental Medicine and Biology, vol 748. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3573-0_14

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