Inherited defects in oxidative phosphorylation Thirteen of the approximately 120 polypeptides required for oxida- tive phosphorylation are coded for by mtDNA and synthesized in mitochondria, whereas the remaining mitochondrial proteins are synthesized in the cytosol and transported into mitochondria. Defects in oxidative phosphorylation are more likely a result of alter- ations in mtDNA, which has a mutation rate about ten times greater than that of nuclear DNA. Tissues with the greatest ATP requirement (for example, central nervous system, skeletal and heart muscle, kidney, and liver) are most affected by defects in oxidative phospho- rylation. Mutations in mtDNA are responsible for several diseases, including some cases of mitochondrial myopathies (Figure 6.16), and Leber hereditary optic neuropathy, a disease in which bilateral loss of central vision occurs as a result of neuroretinal degeneration, including damage to the optic nerve. The mtDNA is maternally inher- ited because mitochondria from the sperm cell do not enter the fertil- ized egg.