Nuclear suppression of mitochondrial defects in cells without the ND6 subunit

Mol Cell Biol. 2006 Feb;26(3):1077-86. doi: 10.1128/MCB.26.3.1077-1086.2006.


Previously, we characterized a mouse cell line, 4A, carrying a mitochondrial DNA mutation in the subunit for respiratory complex I, NADH dehydrogenase, in the ND6 gene. This mutation abolished the complex I assembly and disrupted the respiratory function of complex I. We now report here that a galactose-resistant clone, 4AR, was isolated from the cells carrying the ND6 mutation. 4AR still contained the homoplasmic mutation, and apparently there was no ND6 protein synthesis, whereas the assembly of other complex I subunits into complex I was recovered. Furthermore, the respiratory activity and mitochondrial membrane potential were fully recovered. To investigate the genetic origin of this compensation, the mitochondrial DNA (mtDNA) from 4AR was transferred to a new nuclear background. The transmitochondrial lines failed to grow in galactose medium. We further transferred mtDNA with a nonsense mutation at the ND5 gene to the 4AR nuclear background, and a suppression for mitochondrial deficiency was observed. Our results suggest that change(s) in the expression of a certain nucleus-encoded factor(s) can compensate for the absence of the ND6 or ND5 subunit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Codon, Nonsense
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / metabolism*
  • Frameshift Mutation
  • Galactose / metabolism
  • Membrane Potentials / genetics
  • Mice
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • NADH Dehydrogenase / drug effects*
  • NADH Dehydrogenase / genetics
  • Transfection


  • Codon, Nonsense
  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • NADH dehydrogenase subunit 6, mouse
  • Electron Transport Complex I
  • Galactose