Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly

Chern Lim, Jana Hroudová, Nicole J. Van Bergen, M. Isabel G Lopez Sanchez, Ian A. Trounce, Matthew McKenzie

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2236-2248
Number of pages13
JournalThe FASEB Journal
Issue number6
Publication statusPublished - 1 Jun 2016


  • Blue native PAGE
  • Oxidative phosphorylation
  • Respiratory chain
  • Supercomplex

Cite this