Lookup NU author(s): Professor Rita Horvath
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Complex I (NADH ubiquinone oxidoreductase) is a large multisubunit enzyme that catalyzes the first step in oxidative phosphorylation (OXPHOS). In mammals, complex I biogenesis occurs in a stepwise manner, a process that requires the participation of several nucleus-encoded accessory proteins. The FAD-dependent oxidoreductase-containing domain 1 (FOXRED1) protein is a complex I assembly factor; however, its specific role in the assembly pathway remains poorly understood. We identified a homozygous missense mutation, c. 1308 G -> A (p. V421M) in FOXRED1 in a patient who presented with epilepsy and severe psychomotor retardation. A patient myoblast line showed a severe reduction in complex I, associated with the accumulation of subassemblies centered around similar to 340 kDa, and a milder decrease in complex II, all of which were rescued by retroviral expression of wild-type FOXRED1. Two additional assembly factors, AIFM1 and ACAD9, coimmunoprecipitated with FOXRED1, and all were associated with a 370-kDa complex I subassembly that, together with a 315-kDa subassembly, forms the 550-kDa sub-complex. Loss of FOXRED1 function prevents efficient formation of this midassembly subcomplex. Although we could not identify subassemblies of complex II, our results establish that FOXRED1 function is both broader than expected, involving the assembly of two flavoprotein-containing OXPHOS complexes, and cell type specific.
Author(s): Rendon OZ, Antonicka H, Horvath R, Shoubridge EA
Publication type: Article
Publication status: Published
Journal: Molecular and Cellular Biology
Print publication date: 01/08/2016
Online publication date: 23/05/2016
Acceptance date: 16/05/2016
ISSN (print): 0270-7306
ISSN (electronic): 1098-5549
Publisher: American Society for Microbiology
Altmetrics provided by Altmetric