Normal Function
The MT-CYB gene provides instructions for making a protein called cytochrome b. This protein plays a key role in structures called mitochondria, which convert the energy from food into a form that cells can use. Cytochrome b is one of 11 components of a group of proteins called complex III. In mitochondria, complex III performs one step of a process known as oxidative phosphorylation, in which oxygen and simple sugars are used to create adenosine triphosphate (ATP), the cell's main energy source. During oxidative phosphorylation, the protein complexes, including complex III, drive the production of ATP through a step-by-step transfer of negatively charged particles called electrons. Cytochrome b is involved in the transfer of these particles through complex III.
Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function. Cytochrome b is the only component of complex III that is produced from a gene found in mitochondrial DNA.
Health Conditions Related to Genetic Changes
Mitochondrial complex III deficiency
Mutations in the MT-CYB gene can cause mitochondrial complex III deficiency. When caused by mutations in this gene, the condition is usually characterized by muscle weakness (myopathy) and pain, especially during exercise (exercise intolerance). More severely affected individuals can have problems with other body systems, including the liver, kidneys, heart, and brain.
Most MT-CYB gene mutations that cause mitochondrial complex III deficiency change single protein building blocks (amino acids) in the cytochrome b protein or lead to an abnormally short protein. These cytochrome b alterations impair the formation of complex III, severely reducing the complex's activity and oxidative phosphorylation. Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. It is thought that tissues that require a lot of energy, such as those in the muscles, brain, heart, liver, and kidneys, are most affected by a reduction in oxidative phosphorylation. Damage to these tissues and organs leads to the various features of mitochondrial complex III deficiency.
The location of the MT-CYB gene in mitochondrial DNA (mtDNA) may help explain why some people have more severe features of the condition than others. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). The severity of mitochondrial complex III deficiency caused by MT-CYB gene mutations is thought to be associated with the percentage of mitochondria with the mitochondrial DNA mutation. In most people with MT-CYB-related mitochondrial complex III deficiency, the percentage of mutated mitochondrial DNA is highest in the skeletal muscles, which explains the finding of myopathy in these individuals. It is unclear why the mutation is most prevalent in muscle tissue.
More About This Health ConditionOther Names for This Gene
- COB
- CYTB
- cytochrome b
- cytochrome b (mitochondrion) [Homo sapiens]
- MTCYB
- UQCR3
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Andreu AL, Hanna MG, Reichmann H, Bruno C, Penn AS, Tanji K, Pallotti F, Iwata S, Bonilla E, Lach B, Morgan-Hughes J, DiMauro S. Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA. N Engl J Med. 1999 Sep 30;341(14):1037-44. doi: 10.1056/NEJM199909303411404. Citation on PubMed
- Blakely EL, Mitchell AL, Fisher N, Meunier B, Nijtmans LG, Schaefer AM, Jackson MJ, Turnbull DM, Taylor RW. A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast. FEBS J. 2005 Jul;272(14):3583-92. doi: 10.1111/j.1742-4658.2005.04779.x. Citation on PubMed
- Gil Borlado MC, Moreno Lastres D, Gonzalez Hoyuela M, Moran M, Blazquez A, Pello R, Marin Buera L, Gabaldon T, Garcia Penas JJ, Martin MA, Arenas J, Ugalde C. Impact of the mitochondrial genetic background in complex III deficiency. PLoS One. 2010 Sep 17;5(9):e12801. doi: 10.1371/journal.pone.0012801. Citation on PubMed or Free article on PubMed Central
- Meunier B, Fisher N, Ransac S, Mazat JP, Brasseur G. 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. Citation on PubMed
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