ND6

ND6, or NADH dehydrogenase subunit 6, is a mitochondrial gene encoding one of the core subunits of NADH dehydrogenase (Complex I) of the mitochondrial respiratory chain. It is encoded by the mitochondrial genome (mtDNA) rather than the nuclear genome.

In humans, MT-ND6 is located on the light (L) strand of the circular mtDNA and is transcribed as part of the mitochondrial transcript. The ND6 protein is a small, hydrophobic membrane protein that contributes to electron transfer from NADH to ubiquinone and to proton pumping across the inner mitochondrial membrane, helping to establish the proton motive force used for ATP production.

Mutations in MT-ND6 can cause mitochondrial disease. Among LHON primary mutations, a nucleotide change such as m.14484T>C affecting ND6 has been associated with optic neuropathy, though phenotypes vary and penetrance is incomplete. Other MT-ND6 variants have been reported in a range of mitochondrial disorders. Because mtDNA is maternally inherited and can exist in multiple copies per cell (heteroplasmy), disease expression depends on the proportion of mutant genomes.

Beyond disease, MT-ND6 sequences are used in evolutionary and population studies, as mitochondrial genes provide informative markers for phylogenetics and forensic genetics. The gene is conserved across many animal lineages, reflecting its essential role in cellular energy production.