Mitochondrial DNA Mutations and Diabetes: Another Step toward Individualized Medicine

• DNA, mitochondrial
• Diabetes mellitus
• Deafness
• Hearing loss, sensorineural
• Mutation

Twenty years ago, the mitochondrial chromosome was completely sequenced and the functions of all its genes were identified (1). Those genes code for 13 polypeptides, which are part of the more than 60 polypeptides that form the oxidative phosphorylation and adenosine triphosphate synthetase protein complexes in the inner membrane of the mitochondria. In addition, the mitochondrial chromosome codes for two ribosomal RNAs and 22 transfer RNAs, which participate in the translation of the 13 polypeptides on the mitochondrial ribosomes. Each cell contains hundreds of these chromosomes, and they are transmitted only through the ovum, leading to a maternal inheritance pattern. Inherited and acquired mutations in the mitochondrial chromosome have been implicated in a wide range of human diseases, including neuromuscular disorders, cardiomyopathies, skin lesions, aplastic anemia, Parkinson disease, and aging in general.

In 1992, three groups described several large families with a maternal inheritance pattern of diabetes, sensorineural deafness, or both, as well as a mitochondrial mutation (2-4). This should not have been a great surprise, since family and epidemiologic studies have shown repeatedly that patients with type 2 diabetes mellitus are more likely to have affected mothers than affected fathers and that the disease can be transmitted through several maternal generations (5-7). Apart from mitochondrial DNA mutations, this excess maternal transmission could also result from a maternal diabetic environment in utero that has a metabolic “teratogenic” effect on the fetus, or from the effect of imprinted genes that have a role only when transmitted through the mother. There is support for an in utero effect, in that the risk for diabetes is greater in …