A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure

Nat Genet. 2001 Sep;29(1):57-60. doi: 10.1038/ng706.


Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) catalyzes electron transfer from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11 subunits, of which all but one (cytochrome b) are encoded by nuclear DNA. CIII deficiencies are rare and manifest heterogeneous clinical presentations. Although pathogenic mutations in the gene encoding mitochondrial cytochrome b have been described, mutations in the nuclear-DNA-encoded subunits have not been reported. Involvement of various genes has been indicated in assembly of yeast CIII (refs. 8-11). So far only one such gene, BCS1L, has been identified in human. BCS1L represents, therefore, an obvious candidate gene in CIII deficiency. Here, we report BCS1L mutations in six patients, from four unrelated families and presenting neonatal proximal tubulopathy, hepatic involvement and encephalopathy. Complementation study in yeast confirmed the deleterious effect of these mutations. Mutation of BCS1L would seem to be a frequent cause of CIII deficiency, as one-third of our patients have BCS1L mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain Diseases / genetics*
  • Brain Diseases / pathology
  • Electron Transport Complex III / genetics*
  • Electron Transport*
  • Female
  • Humans
  • Infant, Newborn
  • Kidney Tubules, Proximal / pathology*
  • Liver Failure / genetics*
  • Liver Failure / pathology
  • Male
  • Mitochondria / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Proteins / chemistry
  • Proteins / genetics*
  • Sequence Homology, Amino Acid


  • BCS1L protein, human
  • Proteins
  • ATPases Associated with Diverse Cellular Activities
  • Electron Transport Complex III

Associated data

  • GENBANK/AC079810
  • GENBANK/AF026849