MITOCHONDRIAL-DNA MUTATIONS IN HUMAN DEGENERATIVE DISEASES AND AGING

A wide variety of mitochondrial DNA (mtDNA) mutations have recently be en identified in degenerative diseases of the brain, heart, skeletal m uscle, kidney and endocrine system. Generally, individuals inheriting these mitochondrial diseases are relatively normal in early life, deve lop symptoms during childhood, mid-life, or old age depending on the s everity of the maternally-inherited mtDNA mutation; and then undergo a progressive decline. These novel features of mtDNA disease are propos ed to be the product of the high dependence of the target organs on mi tochondrial bioenergetics, and the cumulative oxidative phosphorylatio n (OXPHOS) defect caused by the inherited mtDNA mutation together with the age-related accumulation mtDNA mutations in post-mitotic tissues.