Oxidative Phosphorylation System: Nuclear Genes and Genetic Disease

Leo Nijtmans, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Lambert van den Heuvel, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Jan AM Smeitink, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Published online: December 2007

DOI: 10.1002/9780470015902.a0006029.pub2

The underlying mutations in nuclear genes that directly affect the mitochondrial oxidative phosphorylation system are now known. Advances in this area have profited from progress in various genome projects.

Keywords: mitochondria; respiratory chain; nuclear gene defects; human

Figure 1. Scheme of the OXPHOS-system in mammalian mitochondria. Electrons (e–) from carbon oxidations (step 1 and dotted lines) are transferred via NADH (step 2) into OXPHOS-complex I (step 3), which is embedded in the lipid bilayer of the mitochondrial inner membrane (IMM), then transported to coenzyme Q (CoQ) (step 4). Some electrons from organic-acid oxidations are transferred, via other flavin-containing enzyme complexes (step 5) directly to CoQ. CoQ delivers electrons via complex III (step 6) and cytochrome c (Cyt c) (step7) to the final electron acceptor complex IV (step 8). Here, oxygen is reduced to water. The electrons lose free energy at each transfer step, and in complexes I, III and IV, the energy is harnessed and coupled to the movement of H+ (step 9 and dashed lines) from the mitochondrial matrix to the intermembrane space (IMS). The proton gradient thus generated is used for the production of ATP by complex V (step 10). Except for complex II, all complexes contain some proteins encoded by the mitochondrial genome and others encoded by the nuclear genome. The number of subunits for each complex is indicated. (CN, cyanide; FMN, flavin mononucleotide; mt, mitochondrial.)
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 Web Links
    ePath Mitochondrial Disorders Overview: http://www.geneclinics.org/profiles/mt-overview/
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    ePath The MitoP2 database. Mitochondrial Proteome Database for mitochondria-related genes, proteins and diseases: http://www.mitop.de:8080/mitop2/

Related Sub-Topics:

Molecular Genetics of Common and Complex Disease | Mitochondrial Diseases | DNA Structure and Function
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Article Title: Oxidative Phosphorylation System: Nuclear Genes and Genetic Disease
 
How to Cite close
Nijtmans, Leo, van den Heuvel, Lambert, and Smeitink, Jan AM(Dec 2007) Oxidative Phosphorylation System: Nuclear Genes and Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006029.pub2]