Contents

MT-ND5

Mitochondrial gene coding for a protein involved in the respiratory chain

ND5
Identifiers
Aliases	ND5, mitochondrially encoded NADH dehydrogenase 5, MTNADH dehydrogenase, subunit 5 (complex I), NADH dehydrogenase subunit 5
External IDs	OMIM: 516005; MGI: 102496; HomoloGene: 36212; GeneCards: ND5; OMA:ND5 - orthologs
Gene location (Human) Chr. Mitochondrial DNA (human)[1] Band n/a Start 12,337 bp[1] End 14,148 bp[1]
Gene location (Mouse) Chr. Mitochondrial DNA (mouse)[2] Band n/a Start 11,742 bp[2] End 13,565 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nasal epithelium postcentral gyrus right ventricle lateral nuclear group of thalamus external globus pallidus ventral tegmental area renal medulla pons cardia Pars compacta Top expressed in central gray substance of midbrain globus pallidus olfactory tubercle temporal lobe paraventricular nucleus of hypothalamus amygdala body of femur nucleus accumbens right ventricle subiculum More reference expression data BioGPS n/a
Gene ontology Molecular function NADH dehydrogenase (ubiquinone) activity oxidoreductase activity NADH dehydrogenase activity Cellular component integral component of membrane mitochondrial inner membrane neuron projection mitochondrial respiratory chain complex I respirasome membrane mitochondrion Biological process ATP synthesis coupled electron transport response to hypoxia response to hydrogen peroxide response to organonitrogen compound mitochondrial respiratory chain complex I assembly mitochondrial electron transport, NADH to ubiquinone Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4540 17721 Ensembl ENSG00000198786 ENSMUSG00000064367 UniProt P03915 P03921 RefSeq (mRNA) n/a n/a RefSeq (protein) n/a NP_904338 Location (UCSC) Chr M: 0.01 – 0.01 Mb Chr M: 0.01 – 0.01 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

MT-ND5 is a gene of the mitochondrial genome coding for the NADH-ubiquinone oxidoreductase chain 5 protein (ND5).^[5] The ND5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.^[6] Variations in human MT-ND5 are associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) as well as some symptoms of Leigh's syndrome and Leber's hereditary optic neuropathy (LHON).^[7][8]

Structure[edit]

MT-ND5 is located in mitochondrial DNA from base pair 12,337 to 14,148.^[5] The MT-ND5 gene produces a 67 kDa protein composed of 603 amino acids.^[9][10] MT-ND5 is one of seven mitochondrial genes encoding subunits of the enzyme NADH dehydrogenase (ubiquinone), together with MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, and MT-ND6. Also known as Complex I, this enzyme is the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centres and the NADH binding site. MT-ND5 and the rest of the mitochondrially encoded subunits are the most hydrophobic of the subunits of Complex I and form the core of the transmembrane region.^[6]

Function[edit]

The MT-ND5 product is a subunit of the respiratory chain Complex I that is supposed to belong to the minimal assembly of core proteins required to catalyze NADH dehydrogenation and electron transfertoubiquinone (coenzyme Q10).^[11] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH₂. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH₂). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.^[6]

Clinical Significance[edit]

A small percentage of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are caused by a G>A mutation at base pair 13513 in the MT-ND5 gene. Mutations in the MT-ND5 gene cause impaired Complex I function of the mitochondrial electron transport system, impairing those tissues that require significant energy input, such as the brain and muscles. Cardiac and renal involvement as well as symptoms such as myopathy and lactic acidosis can also be observed.^[12] Those with MT-ND5 mutations can display the major features of MELAS and MERRF in some patients, as well as symptoms of Leigh's syndrome and/or Leber's hereditary optic neuropathy (LHON) in others.^{[7][8][13][14]}

Interactions[edit]

MT-ND5 interacts with Glutamine synthetase (GLUL), LIG4 and YME1L1.^[5]

References[edit]

External links[edit]

• Mass spectrometry characterization of MT-ND5 at COPaKB
• GeneReviews/NCBI/NIH/UW entry on Mitochondrial DNA-Associated Leigh Syndrome and NARP

This article incorporates text from the United States National Library of Medicine, which is in the public domain.