Mitochondria have important roles in cellular processes, for example, production of cellular energy in the form of ATP and pro¬grammed cell death (apoptosis). Each mitochondrion contains between two and ten copies of mtDNA,. Cells have numerous mitochondria, a cell may harbour several thousand mtDNA copies. Mutations in mtDNA occur at a tenfold or higher rate than in nuclear DNA, possibly due to a high concentration of free oxygen radicals, lack of histones and limited mtDNA repair mechan¬isms.
Diseases caused by mtDNA mutations are numerous, over 150 mutations (including 100 deletions and approximately 50 point mutations) have been identified that are associated with serious human disorders, including myopathies, neu¬rodegenerative diseases, diabetes, cancer and infertility. mtDNA mutations are increasingly implicated in Alzheimer’s, Parkinson’s and Huntington’s diseases.
Typically, a cell contains only one type of mtDNA (homoplasmy). If an individual cell contains two or more types of mtDNA-that is, as a mixture of normal and mutant mtDNA, the phenomenon is known as heteroplasmy. Heteroplasmy allows lethal mutations to persist and most importantly to pass to the next generation. MtDNA is maternally inherited through the egg’s cytoplasm, whereas sperm mitochondria constitute a minor fraction of the zygote’s cohort and are rapidly eliminated after fertilization.
Possibly 1 in 3,500-6000 people has either mtDNA disease or is at risk for development of mtDNA-based disorders, most of which are incurable.
Tachibana et al (2009) Mitochondrial gene replacement in primate offspring and embryonic stem cells. .Nature vol 461 pp 367-372
- Martin Eastwood