MITOCHONDRIAL-DNA AND RNA PROCESSING IN MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-li ke episodes (MELAS), a maternally inherited disorder, is usually assoc iated with a point mutation in mitochondrial DNA (mtDNA) at position 3 ,243 in the tRNA(Leu(UUR)) gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS-3,243 patients. Southern blot analysis showed an increase in the ratio of mtDNA to nuclear DNA in al most all tissues examined, implying that mitochondrial proliferation i s ubiquitous and is not confined to ragged-red fibers in muscle. By no rthern blot analysis, we demonstrated increased steady-state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tR NA(Leu(UUR)) + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and muscle. These results provide further evidence that alter ed mitochondrial nucleic acid metabolism may have pathogenic significa nce in MELAS.