Combined defects in oxidative phosphorylation and fatty acid β-oxidation in Mitochondrial disease
journal contributionposted on 2016-04-01, 00:00 authored by A Nsiah-Sefaa, Matthew McKenzieMatthew McKenzie
Mitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP. Mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis.
Article numberARTN e00313
PublisherPORTLAND PRESS LTD
Publication classificationC Journal article; C1.1 Refereed article in a scholarly journal
Copyright notice2016, The Authors
Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyCell Biologydiseasemitochondriaprotein complex assemblyprotein interactionssupercomplexACYL-COA DEHYDROGENASECOMPLEX-I DEFICIENCYHEREDITARY OPTIC NEUROPATHYCHAIN 3-HYDROXYACYL-COA DEHYDROGENASENADH-UBIQUINONE OXIDOREDUCTASETRIFUNCTIONAL PROTEIN-DEFICIENCYCYTOCHROME-C-OXIDASERESPIRATORY-CHAINIII DEFICIENCYPARKINSONS-DISEASEAnimalsFatty AcidsHumansMitochondrial DiseasesOxidative Phosphorylation