URL of this page: https://medlineplus.gov/genetics/gene/mt-nd5/

MT-ND5 gene

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5
From Genetics Home Reference. Learn more

Normal Function

The MT-ND5 gene provides instructions for making a protein called NADH dehydrogenase 5. This protein is part of a large enzyme complex known as complex I, which is active in mitochondria. 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.

Complex I is one of several enzyme complexes necessary for oxidative phosphorylation. Within mitochondria, these complexes are embedded in a tightly folded, specialized membrane called the inner mitochondrial membrane. During oxidative phosphorylation, mitochondrial enzyme complexes carry out chemical reactions that drive the production of ATP. Specifically, they create an unequal electrical charge on either side of the inner mitochondrial membrane through a step-by-step transfer of negatively charged particles called electrons. This difference in electrical charge provides the energy for ATP production.

Complex I is responsible for the first step in the electron transport process, the transfer of electrons from a molecule called NADH to another molecule called ubiquinone. Electrons are then passed from ubiquinone through several other enzyme complexes to provide energy for the generation of ATP.

Health Conditions Related to Genetic Changes

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Mutations in the MT-ND5 gene are responsible for a small percentage of all cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These mutations alter single DNA building blocks (nucleotides) in the gene. A particular mutation has been identified in at least five people with the characteristic features of MELAS; this mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 13513 (written as G13513A). Most of the MT-ND5 mutations that cause MELAS have been shown to reduce the activity of complex I, which disrupts energy production within mitochondria. Although these abnormalities have the greatest impact on tissues that require a lot of energy (such as the brain and muscles), researchers have not determined how changes in the MT-ND5 gene lead to the specific signs and symptoms of MELAS.

Mutations in the MT-ND5 gene also have been identified in patients with the major features of MELAS in combination with other mitochondrial diseases. For example, researchers have found MT-ND5 mutations in several individuals with the signs of MELAS and some features of Leigh syndrome, a progressive brain disorder that typically appears in infancy or early childhood. In other cases, people with MELAS and a change in the MT-ND5 gene have developed sudden, progressive vision loss characteristic of an eye disease called Leber hereditary optic neuropathy. A few individuals have been reported with signs and symptoms of all three of these mitochondrial conditions—MELAS, Leigh syndrome, and Leber hereditary optic neuropathy.

It is unclear why changes in the MT-ND5 gene can cause such a large variety of signs and symptoms. Even within a single family, affected individuals may have different health problems caused by the same genetic change.

More About This Health Condition

Leigh syndrome

MedlinePlus Genetics provides information about Leigh syndrome

More About This Health Condition

Mitochondrial complex I deficiency

MedlinePlus Genetics provides information about Mitochondrial complex I deficiency

More About This Health Condition

Other disorders

Mutations in the MT-ND5 gene have been identified in at least 10 people with Leigh syndrome. Children with this condition may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. A few affected children with MT-ND5 mutations have had additional features that are not typical of Leigh syndrome, including slow growth before birth (intrauterine growth retardation) and distinctive facial features.

The MT-ND5 mutations responsible for Leigh syndrome change single nucleotides in the gene. These genetic changes disrupt the activity of complex I, impairing the ability of mitochondria to produce energy. It is not known, however, how mutations in the MT-ND5 gene are related to the specific features of Leigh syndrome.

Other Names for This Gene

  • mitochondrially encoded NADH dehydrogenase 5
  • MTND5
  • NADH dehydrogenase subunit 5
  • NADH-ubiquinone oxidoreductase chain 5
  • NADH-ubiquinone oxidoreductase, subunit ND5
  • NADH5
  • ND5
  • NU5M_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Chol M, Lebon S, Bénit P, Chretien D, de Lonlay P, Goldenberg A, Odent S, Hertz-Pannier L, Vincent-Delorme C, Cormier-Daire V, Rustin P, Rötig A, Munnich A. The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. J Med Genet. 2003 Mar;40(3):188-91. Citation on PubMed or Free article on PubMed Central
  • Corona P, Antozzi C, Carrara F, D'Incerti L, Lamantea E, Tiranti V, Zeviani M. A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients. Ann Neurol. 2001 Jan;49(1):106-10. Citation on PubMed
  • Crimi M, Galbiati S, Moroni I, Bordoni A, Perini MP, Lamantea E, Sciacco M, Zeviani M, Biunno I, Moggio M, Scarlato G, Comi GP. A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome. Neurology. 2003 Jun 10;60(11):1857-61. Citation on PubMed
  • Kirby DM, Boneh A, Chow CW, Ohtake A, Ryan MT, Thyagarajan D, Thorburn DR. Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease. Ann Neurol. 2003 Oct;54(4):473-8. Citation on PubMed
  • Liolitsa D, Rahman S, Benton S, Carr LJ, Hanna MG. Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations? Ann Neurol. 2003 Jan;53(1):128-32. Citation on PubMed
  • Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM. Sequence variation in mitochondrial complex I genes: mutation or polymorphism? J Med Genet. 2006 Feb;43(2):175-9. Epub 2005 Jun 21. Citation on PubMed or Free article on PubMed Central
  • Pulkes T, Eunson L, Patterson V, Siddiqui A, Wood NW, Nelson IP, Morgan-Hughes JA, Hanna MG. The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS. Ann Neurol. 1999 Dec;46(6):916-9. Erratum in: Ann Neurol 2000 Jun;47(6):841. Citation on PubMed
  • Santorelli FM, Tanji K, Kulikova R, Shanske S, Vilarinho L, Hays AP, DiMauro S. Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS. Biochem Biophys Res Commun. 1997 Sep 18;238(2):326-8. Citation on PubMed
  • Sudo A, Honzawa S, Nonaka I, Goto YI. Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan. J Hum Genet. 2004;49(2):92-96. doi: 10.1007/s10038-003-0116-1. Epub 2004 Jan 17. Citation on PubMed
  • Valentino ML, Barboni P, Rengo C, Achilli A, Torroni A, Lodi R, Tonon C, Barbiroli B, Fortuna F, Montagna P, Baruzzi A, Carelli V. The 13042G --> A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype. J Med Genet. 2006 Jul;43(7):e38. Citation on PubMed or Free article on PubMed Central
From Genetics Home Reference

Genetics Home Reference has merged with MedlinePlus. Genetics Home Reference content now can be found in the "Genetics" section of MedlinePlus. Learn more

The resources on this site should not be used as a substitute for professional medical care or advice. Users with questions about a personal health condition should consult with a qualified healthcare professional.