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• W2289093606 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 oxidoreductase) steady-state levels were also reduced to 40.3%, possibly due to its diminished stability in the absence of respiratory supercomplex formation. This was in comparison with 143B cybrid controls (that contained wild-type mtDNA on the same nuclear background), which exhibited normal complex I, complex IV, and supercomplex assembly. We conclude that the loss of ND1 stalls complex I assembly during the early stages of its biogenesis, which not only results in the loss of mature complex I but also disrupts the stability of complex IV and the respiratory supercomplex to cause mitochondrial dysfunction.—Lim, S. C., Hroudová, J., Van Bergen, N. J., Lopez Sanchez, M. I. G., Trounce, I. A., McKenzie, M. Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly. FASEB J. 30, 2236–2248 (2016). www.fasebj.org" @default.
• W2289093606 created "2016-06-24" @default.
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• W2289093606 date "2016-02-29" @default.
• W2289093606 modified "2023-10-01" @default.
• W2289093606 title "Loss of mitochondrial DNA‐encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly" @default.
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• W2289093606 doi "https://doi.org/10.1096/fj.201500137r" @default.
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