Compensatory upregulation of respiratory chain complexes III and IV in isolated deficiency of ATP synthase due to TMEM70 mutation
Abstrakt
Mutations in TMEM70 gene represent the most frequent cause of isolated deficiency of mitochondrial ATP synthase resulting in a severe neonatal encephalo-cardiomyopathy. Quantitative analysis of respiratory chain complexes and intramitochondrial proteases was performed in the patient cells with 317-2A>G homozygous mutation in TMEM70 gene.
SDS- and BN-PAGE Western blot analysis revealed a significant 82–89% decrease of ATP synthase and 50–162% increase of respiratory chain complex IV and 22–53% increase of complex III, whereas the content of Lon protease, paraplegin and prohibitins 1 and 2 was not significantly changed. Whole genome expression profiling revealed posttranscriptional origin of the observed adaptive changes in mitochondrial respiratory chain.