Cell Type-Specific Modulation of Respiratory Chain Supercomplex Organization

Int J Mol Sci. 2016 Jun 21;17(6):926. doi: 10.3390/ijms17060926.


Respiratory chain complexes are organized into large supercomplexes among which supercomplex In + IIIn + IVn is the only one that can directly transfer electrons from NADH to oxygen. Recently, it was reported that the formation of supercomplex In + IIIn + IVn in mice largely depends on their genetic background. However, in this study, we showed that the composition of supercomplex In + IIIn + IVn is well conserved in various mouse and human cell lines. Strikingly, we found that a minimal supercomplex In + IIIn, termed "lowest supercomplex" (LSC) in this study because of its migration at the lowest position close to complex V dimers in blue native polyacrylamide gel electrophoresis, was associated with complex IV to form a supercomplex In + IIIn + IVn in some, but not all of the human and mouse cells. In addition, we observed that the 3697G>A mutation in mitochondrial-encoded NADH dehydrogenase 1 (ND1) in one patient with Leigh's disease specifically affected the assembly of supercomplex In + IIIn + IVn containing LSC, leading to decreased cellular respiration and ATP generation. In conclusion, we showed the existence of LSC In + IIIn + IVn and impairment of this supercomplex causes disease.

Keywords: Leigh’s disease; mitochondrial dysfunction; mitochondrial supercomplex; nuclear genetic background; respiratory chain.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Electron Transport Complex II / metabolism*
  • Electron Transport Complex III / metabolism*
  • Female
  • Humans
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Leigh Disease / pathology
  • Male
  • Mice
  • Mitochondria, Liver / metabolism
  • Mutation
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Organ Specificity
  • Protein Multimerization


  • respiratory complex II
  • Adenosine Triphosphate
  • Electron Transport Complex II
  • NADH Dehydrogenase
  • Electron Transport Complex III