Mutations of mitochondrial DNA: the molecular basis of mitochondrial encephalo-myopathies and ageing

The energy consumed by mammalian organisms is mainly generated in mitochondria by respiration-dependent (oxidative) phosphorylation. Mitochondria are partly autonomous cell organelles, because they contain their own DNA (mtDNA). A eukaryotic cell contains hundreds of mitochondria with three to five copies of mtDNA per organelle. In contrast to the nuclear DNA, mtDNA is exclusively maternally inherited (Giles et al., 1980) and in general identical in all cells of a mammalian organism (Greenberg et al., 1983). Recently, in various cases of human mitochondrial diseases, muscle weakness could be correlated with the occurrence of individual respiration-defective cells in the muscle (mitochondrial myopathy). In some cases (Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) deletions or insertions were found in the mtDNA of affected tissues. In a systematic study by Muller-Hocker (1988, 1989) a similar pattern of respiration-deficient cells were also found in muscle, but in particular in the heart of healthy individuals with increasing age. The similar progressive appearance of a mosaic pattern of respiration-defective cells in heart and muscle tissues of KSS and CPEO patients, as well as with increasing age in healthy human beings, suggest a similar molecular mechanism underlying the mitochondrial myopathies and the process of ageing hich results in respiration-defective cells.