STEADY-STATE LEVELS OF MITOCHONDRIAL AND NUCLEAR OXIDATIVE-PHOSPHORYLATION TRANSCRIPTS IN KEARNS-SAYRE SYNDROME

The steady state levels of both mitochondrial and nuclear transcripts were examined in a Kearns-Sayre syndrome patient harboring a heteroplasmic 7.7 kb mitochondrial DNA deletion. Transcripts originating from the genes located outside of the deletion were present in similar amounts to those of control samples, with the transcript levels of each tissue linked to its oxidative phosphorylation capacities. Transcripts originating from genes within the deletion were reduced according to the percentage of mtDNA deleted molecules in the tissue. The fusion transcript resulting from the rearranged genome is expressed in all the tissues tested and its level is related to the amount of the deleted mtDNA. The RNA levels from three nuclear genes encoding two of the Adenine Nucleotide Translocator isoforms (ANT1 and 2) and the beta subunit of the ATPsynthase (ATPsyn beta) were significantly induced in the different tissues independently of the percentage of deleted mtDNA molecules. In contrast, the ANT1 and ATPsyn beta levels were decreased in skeletal muscle. This result could be related to the different distribution of the deleted molecules in tissues.