Six-year prospective follow-up study in 151 carriers of the mitochondrial DNA 3243 A>G variant.

Background: The mitochondrial DNA (mDNA) 3243A>G variant is the most common pathogenic variant of the mDNA. To interpret results of clinical trials in mitochondrial disease, it is important to have a clear understanding of the natural course of disease. To obtain more insight into the disease burden and the progression of disease in carriers of the mDNA 3243 A>G variant, we followed a cohort of 151 carriers from 61 families prospectively for up to 6 years.

Impaired ubiquitin-proteasome-mediated PGC-1α protein turnover and induced mitochondrial biogenesis secondary to complex-I deficiency.

Most eukaryotic cells depend on mitochondrial OXidative PHOSphorylation (OXPHOS) in their ATP supply. The cellular consequences of OXPHOS defects and the pathophysiological mechanisms in related disorders are incompletely understood. Using a quantitative proteomics approach we provide evidence that a genetic defect of complex-I of the OXPHOS system may associate with transcriptional derangements of mitochondrial biogenesis through stabilization of the master transcriptional regulator PPARγ co-activator 1α (PGC-1α) protein.