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 heteropla smic 7.7 kb mitochondrial DNA deletion. Transcripts originating from t he genes located outside of the deletion were present in similar amoun ts to those of control samples, with the transcript levels of each tis sue linked to its oxidative phosphorylation capacities. Transcripts or iginating from genes within the deletion were reduced according to the percentage of mtDNA deleted molecules in the tissue. The fusion trans cript resulting from the rearranged genome is expressed in all the tis sues tested and its level is related to the amount of the deleted mtDN A. 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 diffe rent tissues independently of the percentage of deleted mtDNA molecule s. In contrast, the ANT1 and ATPsyn beta levels were decreased in skel etal muscle. This result could be related to the different distributio n of the deleted molecules in tissues.