Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease

EMBO J. 2007 Jul 11;26(13):3227-37. doi: 10.1038/sj.emboj.7601748. Epub 2007 Jun 7.


In humans, complex I of the respiratory chain is composed of seven mitochondrial DNA (mtDNA)-encoded and 38 nuclear-encoded subunits that assemble together in a process that is poorly defined. To date, only two complex I assembly factors have been identified and how each functions is not clear. Here, we show that the human complex I assembly factor CIA30 (complex I intermediate associated protein) associates with newly translated mtDNA-encoded complex I subunits at early stages in their assembly before dissociating at a later stage. Using antibodies we identified a CIA30-deficient patient who presented with cardioencephalomyopathy and reduced levels and activity of complex I. Genetic analysis revealed the patient had mutations in both alleles of the NDUFAF1 gene that encodes CIA30. Complex I assembly in patient cells was defective at early stages with subunits being degraded. Complementing the deficiency in patient fibroblasts with normal CIA30 using a novel lentiviral system restored steady-state complex I levels. Our results indicate that CIA30 is a crucial component in the early assembly of complex I and mutations in its gene can cause mitochondrial disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Conserved Sequence
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / deficiency
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • NADH Dehydrogenase / chemistry
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Protein Binding
  • Protein Subunits / metabolism
  • Sequence Alignment


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Protein Subunits
  • NADH Dehydrogenase
  • Electron Transport Complex I
  • NDUFAF1 protein, human