Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''ETFDH''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This gene encodes a component of the electron-transfer system in

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and is essential for

electron transfer Electron transfer (ET) occurs when an electron relocates from an atom or molecule to another such chemical entity. ET is a mechanistic description of certain kinds of redox reactions involving transfer of electrons. Electrochemical processes ar ...

from a number of mitochondrial flavin-containing

dehydrogenase A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as f ...

s to the main respiratory chain.

Function

Electron-transferring-flavoprotein dehydrogenase in the

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

accepts electrons from electron-transfer flavoprotein which is located in the

mitochondrial matrix In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribo ...

and reduces

ubiquinone Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10. It is a 1,4-benzoq ...

in the mitochondrial membrane. Deficiency in electron-transferring-flavoprotein dehydrogenase have been demonstrated in some patients with type II glutaric aciduria.

Structure

The ''ETFDH'' gene is located on the q arm of

chromosome 4 Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs (the building material of DNA) and represents between 6 and 6.5 percent of the t ...

in position 32.1 and has 13

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s spanning 36,613 base pairs. The protein is synthesized as a 67-kDa

precursor Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of unr ...

which is targeted to mitochondria and processed in a single step to a 64-kDa mature form located in the mitochondrial membrane. This 64-kDA mature form is a monomer integrated into the mitochondrial inner membrane, containing a 4Fe-4S cluster and 1 molecule of

FAD A fad or trend is any form of collective behavior that develops within a culture, a generation or social group in which a group of people enthusiastically follow an impulse for a short period. Fads are objects or behaviors that achieve short- ...

Function

This enzyme, along with electron transfer flavoprotein (ETF), is required for electron transfer from more than 9 mitochondrial flavin-containing dehydrogenases to the main respiratory chains. It accepts electrons from ETF and reduces ubiquinone.

Clinical Significance

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s in the ''ETFDH'' can cause glutaric aciduria 2C (GA2C), an autosomal recessively inherited disorder of

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

, and

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but re ...

metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of

glutaric acid Glutaric acid is the organic compound with the formula C3H6(COOH)2 . Although the related "linear" dicarboxylic acids adipic and succinic acids are water-soluble only to a few percent at room temperature, the water-solubility of glutaric acid is ...

, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. A c.250G>A (p.Ala84Thr) mutation, the most common mutation in the ''ETFDH'' gene, causes increased production of

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS) and shortened

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

s in cells expressing this mutant compared to

wild type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...

cells. Suberic acid, an accumulated intermediate

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

in dehydrogenase deficiency, can significantly impair neurite outgrowth in NSC34 cells. This shortening of neurites can be restored by

riboflavin Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in ...

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...

, or

Coenzyme Q10 Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10. It is a 1,4-benzoq ...

supplements.

Interactions

The encoded protein interacts with

MYH7B Myosin-7B also known as myosin, heavy chain 7B is a protein that in humans is encoded by the ''MYH7B'' gene. Function MYH7B is a slow-twitch myosin Myosins () are a superfamily of motor proteins best known for their roles in muscle contr ...

, LINC00174,

LINC00574 The LINC (Laboratory INstrument Computer) is a 12-bit, 2048-word transistorized computer. The LINC is considered by some the first minicomputer and a forerunner to the personal computer. Originally named the "Linc", suggesting the project's o ...

, Homeobox protein goosecoid-2,

AIRE Aire may refer to: Music * ''Aire'' (Yuri album), 1987 * ''Aire'' (Pablo Ruiz album), 1997 *''Aire (Versión Día)'', an album by Jesse & Joy Places *Aire-sur-la-Lys, a town in the Pas-de-Calais département in France *Aire-la-Ville, a municip ...

OTX1 Homeobox protein OTX1 is a protein that in humans is encoded by the ''OTX1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...

, Keratin-associated protein 13-2, Keratin-associated protein 11-1,

TRIM69 Tripartite motif containing 69 is a protein that in humans is encoded by the TRIM69 gene. Function This gene encodes a member of the RING-B-box-coiled-coil (RBCC) family and encodes a protein with an N-terminal RING finger motif, a PRY domain ...

, Zinc finger protein 581, and

COX6B1 Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the ''COX6B1'' gene. Cytochrome ''c'' oxidase 6B1 is a subunit of the cytochrome ''c'' oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial ele ...

Function

Structure

Function

Clinical Significance

Interactions

References

Further reading