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

• Published in: Biochimica et biophysica acta Vol. 1827; no. 11-12; pp. 1346 - 1361
• Main Authors: Meunier, B., Fisher, N., Ransac, S., Mazat, J.-P., Brasseur, G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2013
• Subjects: bc1 complex; BCS1 BCS1L; Complex III mutations; Electron Transport - genetics; Electron Transport Complex III - chemistry; Electron Transport Complex III - genetics; Electron Transport Complex III - metabolism; Human myopathy; Humans; Mitochondrial cytochrome b; 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; Yeast Saccharomyces cerevisiae; Yeast Saccharomyces cerevisiae; Sub; haem bL; ISP; haem bH; BCS1 BCS1L; CI-V; a.a; ROS; LHON; Qi; bc1 complex; Human myopathy; MELAS; Complex III mutations; Qo; cyt; Mitochondrial cytochrome b; Reactive Oxygen Species; high mid-point potential cyt b haem; cytochrome; Rieske or Iron Sulfur Protein; quinol oxidising site on the positive side of the membrane; haem b(H); haem b(L); low mid-point potential cyt b haem; subunit; Leber Hereditary Optic Neuropathy; Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes; bc complex; Q(i); Q(o); quinone reductase site on the negative side of the membrane; complex I-V; amino-acid
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/j.bbabio.2012.11.015

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.
► Exhaustive list of mutations in human mitochondrial cytochrome b. ► Mutations in the assembly factors (ex. BCS1L) essential for complex III functionality. ► Description of the medical aspects important for clinicians. ► Use of yeast as a model to study human myopathies and associated diseases. ► Analysis of the human and yeast mutations in the atomic structure of bc1 complex.