ROLE OF THE MITOCHONDRIAL-DNA AND CALMITINE IN MYOPATHIES

We present data on mitochondrial DNA deletions and mitochondrial disea ses. The mechanism of their occurrence is discussed on the basis of de letion breakpoints and particularly with the slippage mispairing hypot hesis. As the correlation between the genotypes and the phenotypes is not always straightforward, a classification of mitochondrial diseases is suggested according to the genotype (deletions, depletions and dup lications, mutations affecting structural genes or tRNA genes) rather than the phenotype. The effect of mitochondrial DNA alterations on the expression of nuclear encoded proteins is presented, and the nucleus can be found to respond differently but in a coordinate way according to the kind of mitochondrial DNA alteration. The search for a nuclear gene affecting the expression of Leber's disease could not show any co rrelation between the alleles of TAP2 (transporter antigen peptide) an d the expression of the disease. Finally, we present new data on anoth er class of myopathies, namely Duchenne muscular dystrophy (DMD), wher e mitochondria could play an unexpected role in the metabolism of calc ium. In some patients with DMD a mitochondrial calcium binding protein that is mainly located in the mitochondrial matrix and which is named 'calmitine' was found to disappear. We have thus cloned its cDNA and found that it was identical with to calsequestrine which is a high-cap acity but low-affinity Ca2+ binding protein from the sarcoplasmic reti culum.