Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases

Biochim Biophys Acta. 2013 Nov-Dec;1827(11-12):1346-61. doi: 10.1016/j.bbabio.2012.11.015. Epub 2012 Dec 5.


The bc1 complex or complex III is a central component of the aerobic respiratory chain in prokaryotic and eukaryotic organisms. It catalyzes the oxidation of quinols and the reduction of cytochrome c, establishing a proton motive force used to synthesize adenosine triphosphate (ATP) by the F1Fo ATP synthase. In eukaryotes, the complex III is located in the inner mitochondrial membrane. The genes coding for the complex III have a dual origin. While cytochrome b is encoded by the mitochondrial genome, all the other subunits are encoded by the nuclear genome. In this review, we compile an exhaustive list of the known human mutations and associated pathologies found in the mitochondrially-encoded cytochrome b gene as well as the fewer mutations in the nuclear genes coding for the complex III structural subunits and accessory proteins such as BCS1L involved in the assembly of the complex III. Due to the inherent difficulties of studying human biopsy material associated with complex III dysfunction, we also review the work that has been conducted to study the pathologies with the easy to handle eukaryotic microorganism, the yeast Saccharomyces cerevisiae. Phenotypes, biochemical data and possible effects due to the mutations are also discussed in the context of the known three-dimensional structure of the eukaryotic complex III. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.

Keywords: BCS1 BCS1L; CI-V; Complex III mutations; Human myopathy; ISP; LHON; Leber Hereditary Optic Neuropathy; MELAS; Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes; Mitochondrial cytochrome b; Q(i); Q(o); ROS; Reactive Oxygen Species; Rieske or Iron Sulfur Protein; Sub; Yeast Saccharomyces cerevisiae; a.a.; amino-acid; bc(1) complex; complex I-V; cyt; cytochrome; haem b(H); haem b(L); high mid-point potential cyt b haem; low mid-point potential cyt b haem; quinol oxidising site on the positive side of the membrane; quinone reductase site on the negative side of the membrane; subunit.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Electron Transport / genetics
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / genetics
  • Electron Transport Complex III / metabolism*
  • Humans
  • Mitochondrial Myopathies / genetics
  • Mitochondrial Myopathies / metabolism*
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Electron Transport Complex III