NDUFA4, mitochondrial complex associated is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the NDUFA4

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The NDUFA4 protein was first described to be a subunit of

NADH dehydrogenase (ubiquinone) Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes th ...

, which is located in the

mitochondrial inner 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 ...

and is the largest of the five complexes of the

electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...

. However, recent research has described NDUFA4 as a subunit of cytochrome ''c'' oxidase. Mutations in the NDUFA4 gene are associated with

Leigh's syndrome Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who firs ...

Structure

The NDUFA4 gene is located on the p arm of

chromosome 7 Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...

at position 21.3 with a total length of 8,234 base pairs. The NDUFA4 gene produces a 9.4 kDa protein composed of 81

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. NDUFA4 has traditionally been defined as a subunit of the enzyme

(Complex I), the largest of the respiratory complexes. More recent research has demonstrated that no perturbation of

Complex I Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes th ...

occurs upon NDUFA4 deletion, calling into question its role in this complex. It has been demonstrated that NDUFA4 plays a role in

Complex IV The enzyme cytochrome c oxidase or Complex IV (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and the mitochondria of eukaryotes. It is the last enzyme in the respiratory ele ...

function and biogenesis, however, with some authors suggesting that the NDUFA4 gene be renamed and the structure of both

and

be re-evaluated.

Clinical significance

Mutations in the NDUFA4 gene can result in

, a severe neurological disorder that typically arises in the first year of life. Disruption of

, also called cytochrome c oxidase or COX, is the most common cause of Leigh syndrome. Given that NDUFA4 has only recently been identified as a subunit of

rather than

, patients with previously unexplained COX deficiencies could be genetically tested for NDUFA4 mutations.

Interactions

NDUFA4 has many protein-protein interactions, including ubiquitin proteins such as

ubiquitin C Polyubiquitin-C is a protein encoded by the ''UBC'' gene in humans. Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A. ''UBC'' gene is one of the two stress-regulated polyubiquitin genes (''UBB'' and ''UBC' ...

and

UBL4A Ubiquitin-like protein 4A is a protein that in humans is encoded by the ''UBL4A'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that i ...

, as well as

CUL3 Cullin 3 is a protein that in humans is encoded by the ''CUL3'' gene. Cullin 3 protein belongs to the family of cullins which in mammals contains eight proteins (Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7 and Cullin 9 ...

and

PARK7 DJ1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the ''PARK7'' gene. Its weak glyoxalase activity has been verified by many labs, however the reported protein deglycase activity is likely to be an artifact ...

Structure

Clinical significance

Interactions

References

Further reading