Mitochondrial complex I deficiency of nuclear origin I. Structural genes

Mol Genet Metab. 2012 Feb;105(2):163-72. doi: 10.1016/j.ymgme.2011.11.188. Epub 2011 Nov 18.


Complex I (or NADH-ubiquinone oxidoreductase), is by far the largest respiratory chain complex with 38 subunits nuclearly encoded and 7 subunits encoded by the mitochondrial genome. Its deficiency is the most frequently encountered in mitochondrial disorders. Here, we summarize recent data obtained on architecture of complex I, and review the pathogenic mutations identified to date in nuclear structural complex I genes. The structural NDUFS1, NDUFS2, NDUFV1, and NDUFS4 genes are mutational hot spot genes for isolated complex I deficiency. The majority of the pathogenic mutations are private and the genotype-phenotype correlation is inconsistent in the rare recurrent mutations.

Publication types

  • Review

MeSH terms

  • Electron Transport
  • Electron Transport Complex I / chemistry*
  • Electron Transport Complex I / deficiency
  • Electron Transport Complex I / genetics
  • Genetic Association Studies
  • Humans
  • Mitochondria / enzymology*
  • Mitochondrial Diseases / enzymology*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*


  • Mitochondrial Proteins
  • NDUFS1 protein, human
  • NDUFV1 protein, human
  • Nuclear Proteins
  • NADH Dehydrogenase
  • Electron Transport Complex I
  • NDUFS2 protein, human
  • NDUFS4 protein, human

Supplementary concepts

  • Mitochondrial complex I deficiency