In humans, mutations in MT-CO1 have been associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.
[6] Proton pumping heme-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes.
The CuB-heme a3 (or heme o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (EC 1.10.3.10), is directly involved in the coupling between dioxygen reduction and proton pumping.
[13] A related nitric-oxide reductase (EC 1.7.99.7) exists in denitrifying species of archaea and eubacteria and is a heterodimer of cytochromes b and c. Phenazine methosulphate can act as acceptor.
It has been suggested that cytochrome c oxidase catalytic subunits evolved from ancient nitric oxide reductases that could reduce both nitrogen and oxygen.
[18][19] Mutations in this gene in humans are associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.
[8][9][10] LHON, correlated with mutations in MT-CO1, is characterized by optic nerve dysfunction, causing subacute or acute central vision loss.
Because this disease is a result of mitochondrial DNA mutations affecting the respiratory chain complexes, it is inherited maternally.
[23][24][9][10] MT-CO1 mutations play a role in colorectal cancer, a very complex disease displaying malignant lesions in the inner walls of the colon and rectum.
Long-standing ulcerative colitis, colon polyps, and family history are risk factors for colorectal cancer.
Affected individuals manifest progressive, postlingual, sensorineural hearing loss involving high frequencies.
[32] On average, the percent of colonic crypts deficient for MT-COI reaches 18% in women and 23% in men by 80–84 years of age.
[35] The occurrence of frequent crypts with almost complete loss of MT-COI in their 1700 to 5,000 cells suggests a process of natural selection.
However, it has also been shown that a deficiency throughout a particular crypt due to an initial mitochondrial DNA mutation may occasionally occur through a stochastic process.
[32] This illustrates that clones of deficient crypts often arise, and thus that there is likely a positive selective bias that has allowed them to spread in the human colonic epithelium.
One suggestion[32] is that deficiency of MT-COI in a mitochondrion leads to lower reactive oxygen production (and less oxidative damage) and this provides a selective advantage in competition with other mitochondria within the same cell to generate homoplasmy for MT-COI-deficiency.
Within the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, the encoded protein interacts with COA3 and SMIM20/MITRAC7.