Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency caused by SURF1 gene mutations
Abstract
SURF1 gene mutations are frequent cause of severe assembly defects of cytochrome c oxidase (COX) with clinical manifestation of Leigh syndrome. In this study, fibroblasts cell lines from patients with different SURF1 mutations were analyzed to investigate changes in protein and transcript levels of OXPHOS complexes and other pro-mitochondrial genes due to SURF1 mutations.
Immunoblott analysis revealed decreased amount of COX accompanied by compensatory increase of respiratory chain complexes I, III and V. Altered biogenesis of COX resulted in accumulation of COX assembly intermediates.
In patient cells the residual COX was incorporated predominantly into I-III2-IV1 supercomplex. Whole genome expression profiling showed general decrease of transcriptional activity in patients cells and indicated that observed compensatory changes in OXPHOS complexes originate from posttranscriptional mechanisms.