title: Molecular base of biochemical complex I deficiency.
abstract: The oxidative phosphorylation (OXPHOS) system, consisting of five enzyme complexes (I-V) together with 2 electron carriers, has an important role in the energy metabolism of the cell. With 45 subunits, complex I is the first and largest complex of the respiratory chain. It is under bigenomic control and a proper interaction between the mitochondrial and the nuclear genome is important for a good biogenesis and functioning of the complex. Isolated complex I deficiency is the most frequently diagnosed form of mitochondrial disorders caused by the disturbance of the OXPHOS system. It has a wide clinical variety and, at present, in many patients the underlying genetic cause of the complex I deficiency is still not known. In this review, the role of complex I in the oxidative phosphorylation and the localization and function of the different complex I subunits will be described. Furthermore, a brief overview of the assembly process and biochemical studies, performed when a patient is suspected of a mitochondrial disorder is given. Finally, the present knowledge for molecular base of complex I deficiency is described and the findings in a research cohort of patients with complex I deficiency are reported. Identifying new genes encoding proteins involved in complex I biogenesis is challenging and in the near future new powerful techniques will make high throughput screening possible. Progress in elucidating the genetic defect causing complex I deficiencies is important for a better genetic counseling, prenatal diagnostic possibilities and further development of new treatment strategies to cure the complex I deficiencies in the future.
authors: Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Saskia J G
authors: SJ
authors: Hoefs
authors: Richard J
authors: RJ
authors: Rodenburg
authors: Jan A M
authors: JA
authors: Smeitink
authors: Lambert P
authors: LP
authors: van den Heuvel
mesh_terms: D042967:Electron Transport Complex I / Q000172:deficiency* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics*
chemical_list: D042967:Electron Transport Complex I