Journal article
Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly
SC Lim, J Hroudová, NJ Van Bergen, MIG Lopez Sanchez, IA Trounce, M McKenzie
FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2016
Abstract
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) must be assembled precisely from 45 protein subunits for it to function correctly. One of its mitochondrial DNA (mtDNA) encoded subunits, ND1, is incorporated during the early stages of complex I assembly. However, little is known about how mutations in ND1 affect this assembly process. We found that in human 143B cybrid cells carrying a homoplasmic MT-ND1 mutation, ND1 protein could not be translated. As a result, the early stages of complex I assembly were disrupted, with mature complex I undetectable and complex I-linked respiration severely reduced to 2.0% of control levels. Interestingly, complex IV (ferrocytochrome c:oxygen oxido..
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Awarded by Australian Research Council
Funding Acknowledgements
This work was supported in part by the Poxon Neurosurgical Foundation (to M. M. and I. A. T.), the Australian National Health and Medical Research Council (APP1061472 to I. A. T.), the Wagstaff Bequest of the Royal Victorian Eye and Ear Hospital (to I. A. T.), the Australian Research Council Future Fellowship Scheme (to M. M.), the William Buckland Foundation (to M. M.), Monash University (to M. M.), a Group of Eight Fellowship (to J. H.), and Czech Republic award PRVOUK-P26/LF1/4 (to J. H.). The Centre for Eye Research Australia and the Hudson Institute of Medical Research receive support from the Victorian Government Infrastructure Program.