title: Mitochondrial cytochrome c oxidase deficiency.
abstract: 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.
authors: 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.
authors: Malgorzata
authors: M
authors: Rak
authors: 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.
authors: Paule
authors: P
authors: Bénit
authors: 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.
authors: Dominique
authors: D
authors: Chrétien
authors: 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.
authors: Juliette
authors: J
authors: Bouchereau
authors: 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.
authors: Manuel
authors: M
authors: Schiff
authors: American University of Beirut Medical Center, Department of Pathology and Laboratory Medicine, Cairo Street, Hamra, Beirut, Lebanon.
authors: Riyad
authors: R
authors: El-Khoury
authors: Biological Sciences Department, Columbia University, New York, NY 10027, U.S.A.
authors: Alexander
authors: A
authors: Tzagoloff
authors: 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 pierre.rustin@inserm.fr.
authors: Pierre
authors: P
authors: Rustin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure
chemical_list: D003576:Electron Transport Complex IV
keywords: cytochrome c oxidase; genetic diseases; mitochondria; mitochondrial diseases; mtDNA; signalling pathway