Location of theMT-CO3 gene in the human mitochondrial genome.MT-CO3 is one of the three cytochrome c oxidase subunit mitochondrial genes (orange boxes).
Protein family
Cytochrome c oxidase subunit III
Structure of the 13-subunit oxidized cytochrome c oxidase.[5]
TheMT-CO3 gene produces a 30 kDa protein composed of 261amino acids.[10][11] COX3, the protein encoded by this gene, is a member of thecytochrome c oxidase subunit 3 family. This protein is located on theinner mitochondrial membrane. COX3 is a multi-pass transmembrane protein: in human, it contains 7transmembrane domains at positions 15–35, 42–59, 81–101, 127–147, 159–179, 197–217, and 239–259.[8][9]
Cytochrome c oxidase (EC1.9.3.1) is the terminal enzyme of the respiratory chain ofmitochondria and many aerobic bacteria. It catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen:
This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane.[12][13]
Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits,I,II andIII. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small subunits.[14]
As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Although the cytochrome o oxidases do not catalyze the cytochrome c but the quinol (ubiquinol) oxidation they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits:subunit I is the most conserved subunit, whereassubunit II is the least conserved.[15][16][17]
LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due tooptic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. Mutations at positions 9438 and 9804, which result inglycine-78 toserine andalanine-200 tothreonineamino acid changes, have been associated with this disease.[18][8][9]
Recurrent myoglobinuria is characterized by recurrent attacks ofrhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion ofmyoglobin in the urine. It has been associated with mitochondrial complex IV deficiency.[20][8][9]
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