Mitochondrial DNA and Disease

Abstract

Mitochondrial diseases are a group of disorders characterized by morphological or functional defects of the mitochondria, the organelles producing most of our cellular energy. As the only extranuclear site carrying genetic information, the mitochondria add an important chapter into the inheritance patterns of genetic diseases. Mitochondrial DNA (mtDNA) is exclusively maternally inherited in humans, but a mitochondrial disorder may follow either maternal or Mendelian inheritance, depending on the site of the primary gene defect. After the initial finding of mtDNA mutations in rare ocular myopathies in 1988, an explosion in the amount of information on mitochondrial diseases has occurred. Because the mitochondria produce energy in all the tissues, symptoms resulting from mtDNA mutations may originate from any organ system, and the clinical spectrum of mitochondrial diseases has expanded to virtually all branches of medicine. Subgroups of several common diseases, such as diabetes, deafness and inherited cardiomyopathies, have been found to be caused by mtDNA mutations, and some mtDNA defects have been suggested to modify the outcome of diseases primarily caused by other factors, such as Parkinson's or Alzheimer's disease. Although no breakthroughs in the therapeutic trials on the devastating mitochondrial diseases have so far been achieved, detection of mtDNA mutations offers an accurate diagnosis and is a prerequisite for genetic counselling, being now accessible to most clinicians.