Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

MT-ATP6

Reviewed October 2011

What is the official name of the MT-ATP6 gene?

The official name of this gene is “mitochondrially encoded ATP synthase 6.”

MT-ATP6 is the gene's official symbol. The MT-ATP6 gene is also known by other names, listed below.

What is the normal function of the MT-ATP6 gene?

The MT-ATP6 gene provides information for making a protein that is essential for normal mitochondrial function. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. These cellular structures produce energy through a process called oxidative phosphorylation, which uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.

The MT-ATP6 protein forms one part (subunit) of a large enzyme called ATP synthase. This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation. Specifically, one segment of ATP synthase allows positively charged particles, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP.

Does the MT-ATP6 gene share characteristics with other genes?

The MT-ATP6 gene belongs to a family of genes called mitochondrial respiratory chain complex (mitochondrial respiratory chain complex).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the MT-ATP6 gene related to health conditions?

Leigh syndrome - caused by mutations in the MT-ATP6 gene

Mutations in the MT-ATP6 gene have been found in approximately 10 to 20 percent of people with Leigh syndrome. Leigh syndrome is a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience delayed development, muscle weakness, problems with movement, or difficulty breathing.

MT-ATP6 gene mutations associated with Leigh syndrome change one DNA building block (nucleotide) in the MT-ATP6 gene. The most common genetic change replaces the nucleotide thymine with the nucleotide guanine at position 8993 (written as T8993G). The mutations that cause Leigh syndrome impair the function or stability of the ATP synthase complex, inhibiting ATP production and impairing oxidative phosphorylation.

Although the exact mechanism is unclear, researchers believe that impaired oxidative phosphorylation can lead to cell death because of decreased energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in the brain likely causes the characteristic changes in the brain seen in Leigh syndrome, which contribute to the signs and symptoms of the condition. Cell death in other sensitive tissues may also contribute to the features of Leigh syndrome.

neuropathy, ataxia, and retinitis pigmentosa - caused by mutations in the MT-ATP6 gene

Some of the mutations that cause Leigh syndrome are also responsible for a similar, but less severe, condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). A small number of mutations in the MT-ATP6 gene have been identified in people with NARP. Each of these mutations changes one nucleotide in the MT-ATP6 gene. As in Leigh syndrome, the most common genetic change associated with NARP replaces the nucleotide thymine with the nucleotide guanine at position 8993 (written as T8993G). The mutations that cause NARP alter the structure or function of ATP synthase, reducing the ability of mitochondria to produce ATP. Although the precise effects of these mutations are unclear, researchers continue to investigate how changes in the MT-ATP6 gene interfere with ATP production and lead to muscle weakness, vision loss, and the other features of NARP.

Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. People with Leigh syndrome due to a MT-ATP6 gene mutation tend to have a very high percentage of mitochondria with the mutation (from more than 90 percent to 95 percent). The less-severe features of NARP result from a lower percentage of mitochondria with the mutation, typically 70 percent to 90 percent. Because these two conditions result from the same genetic changes and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.

other disorders - caused by mutations in the MT-ATP6 gene

A condition called familial bilateral striatal necrosis, which is similar to Leigh syndrome, can also result from changes in the MT-ATP6 gene. In the few reported cases with these mutations, affected children have had delayed development, problems with movement and coordination, weak muscle tone (hypotonia), and an unusually small head size (microcephaly). Researchers have not determined why MT-ATP6 mutations result in this combination of signs and symptoms in children with bilateral striatal necrosis.

Where is the MT-ATP6 gene located?

The MT-ATP6 gene is located in mitochondrial DNA.

Molecular Location in mitochondrial DNA: base pairs 8,526 to 9,206

Overview of gene located on mitochondrial DNA Close-up of gene located on mitochondrial DNA

Where can I find additional information about MT-ATP6?

You and your healthcare professional may find the following resources about MT-ATP6 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the MT-ATP6 gene or gene products?

  • ATP6
  • ATP6_HUMAN
  • ATPASE6
  • ATPase-6
  • ATPase protein 6
  • ATP synthase 6
  • ATP synthase F0 subunit 6
  • MTATP6
  • Su6m

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding MT-ATP6?

adenosine diphosphate ; adenosine triphosphate ; ADP ; ataxia ; ATP ; bilateral ; cell ; charged particles ; DNA ; enzyme ; familial ; gene ; guanine ; hypotonia ; microcephaly ; mitochondria ; molecule ; muscle tone ; mutation ; necrosis ; neuropathy ; nucleotide ; oxidative phosphorylation ; oxygen ; phosphorylation ; protein ; proton ; spectrum ; striatal ; subunit ; syndrome ; thymine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • De Meirleir L, Seneca S, Lissens W, Schoentjes E, Desprechins B. Bilateral striatal necrosis with a novel point mutation in the mitochondrial ATPase 6 gene. Pediatr Neurol. 1995 Oct;13(3):242-6. (http://www.ncbi.nlm.nih.gov/pubmed/8554662?dopt=Abstract)
  • Gene Review: Mitochondrial DNA-Associated Leigh Syndrome and NARP (http://www.ncbi.nlm.nih.gov/books/NBK1173)
  • Lenaz G, Baracca A, Carelli V, D'Aurelio M, Sgarbi G, Solaini G. Bioenergetics of mitochondrial diseases associated with mtDNA mutations. Biochim Biophys Acta. 2004 Jul 23;1658(1-2):89-94. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15282179?dopt=Abstract)
  • Mattiazzi M, Vijayvergiya C, Gajewski CD, DeVivo DC, Lenaz G, Wiedmann M, Manfredi G. The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants. Hum Mol Genet. 2004 Apr 15;13(8):869-79. Epub 2004 Mar 3. (http://www.ncbi.nlm.nih.gov/pubmed/14998933?dopt=Abstract)
  • Moslemi AR, Darin N, Tulinius M, Oldfors A, Holme E. Two new mutations in the MTATP6 gene associated with Leigh syndrome. Neuropediatrics. 2005 Oct;36(5):314-8. (http://www.ncbi.nlm.nih.gov/pubmed/16217706?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4508)
  • Schon EA, Santra S, Pallotti F, Girvin ME. Pathogenesis of primary defects in mitochondrial ATP synthesis. Semin Cell Dev Biol. 2001 Dec;12(6):441-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11735378?dopt=Abstract)
  • Sgarbi G, Baracca A, Lenaz G, Valentino LM, Carelli V, Solaini G. Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA. Biochem J. 2006 May 1;395(3):493-500. (http://www.ncbi.nlm.nih.gov/pubmed/16402916?dopt=Abstract)
  • Thyagarajan D, Shanske S, Vazquez-Memije M, De Vivo D, DiMauro S. A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis. Ann Neurol. 1995 Sep;38(3):468-72. (http://www.ncbi.nlm.nih.gov/pubmed/7668837?dopt=Abstract)
  • Uziel G, Moroni I, Lamantea E, Fratta GM, Ciceri E, Carrara F, Zeviani M. Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families. J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):16-22. (http://www.ncbi.nlm.nih.gov/pubmed/9221962?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2011
Published: November 24, 2014