As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.
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Cover Image
Cover Image
Image of immunofluroscence staining of mouse gonads (left – testis and right – ovary) attached to the mesonephros from between embryonic day 12 and 13. Green indicates the sertoli cell protein Anti-Mullerain Hormone (AMH) and red indicates the ovarian protein called Foxl2. Blue indicates DAPI (which stains the nucleus). The antibodies are AMH (MIS) E19 santa Cruz, sc-34833 and Foxl2 Novus NB100-1277. For further details please see pp. 421-432. The image was kindly generated and provided by I. Knarston, K. Ayers and A. Sinclair.
Review Article|
February 04 2016
Mitochondrial cytochrome c oxidase deficiency
Malgorzata Rak;
Malgorzata Rak
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
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Paule Bénit;
Paule Bénit
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
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Dominique Chrétien;
Dominique Chrétien
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
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Juliette Bouchereau;
Juliette Bouchereau
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
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Manuel Schiff;
Manuel Schiff
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
‡Reference Center for Inherited Metabolic Diseases, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 48 Boulevard Sérurier, 75019 Paris, France
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Riyad El-Khoury;
Riyad El-Khoury
§American University of Beirut Medical Center, Department of Pathology and Laboratory Medicine, Cairo Street, Hamra, Beirut, Lebanon
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Alexander Tzagoloff;
Alexander Tzagoloff
║Biological Sciences Department, Columbia University, New York, NY 10027, U.S.A.
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Pierre Rustin
*Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1141, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
†Faculté de Médecine Denis Diderot, Université Paris Diderot–Paris 7, Site Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France
Correspondence: Pierre Rustin (email [email protected]).
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Publisher: Portland Press Ltd
Received:
October 05 2015
Revision Received:
November 11 2015
Accepted:
November 20 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (6): 393–407.
Article history
Received:
October 05 2015
Revision Received:
November 11 2015
Accepted:
November 20 2015
Citation
Malgorzata Rak, Paule Bénit, Dominique Chrétien, Juliette Bouchereau, Manuel Schiff, Riyad El-Khoury, Alexander Tzagoloff, Pierre Rustin; Mitochondrial cytochrome c oxidase deficiency. Clin Sci (Lond) 1 March 2016; 130 (6): 393–407. doi: https://doi.org/10.1042/CS20150707
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