Prevalence of oral corticosteroid use in the German severe asthma population.

Aims: We investigated the prevalence of severe asthma, its comorbidities, and especially the use of oral corticosteroid (OCS) therapy in patients with severe asthma.

Methods: Pooled data from 3 961 429 patients insured (with statutory health insurance) during the year 2015 were analysed. Prevalence rates of severe asthma and its OCS-associated comorbidities in patients on high-dosage (HD) inhaled corticosteroid (ICS) in combination with a long-acting β agonist (LABA) therapy were compared with those of patients who were also treated with OCSs.

Translation and Assembly of Radiolabeled Mitochondrial DNA-Encoded Protein Subunits from Cultured Cells and Isolated Mitochondria.

In higher eukaryotes, the mitochondrial electron transport chain consists of five multi-subunit membrane complexes responsible for the generation of cellular ATP. Of these, four complexes are under dual genetic control as they contain subunits encoded by both the mitochondrial and nuclear genomes, thereby adding another layer of complexity to the puzzle of respiratory complex biogenesis. These subunits must be synthesized and assembled in a coordinated manner in order to ensure correct biogenesis of different respiratory complexes.

MTO1 mediates tissue specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention.

Mitochondrial diseases often exhibit tissue-specific pathologies, but this phenomenon is poorly understood. Here we present regulation of mitochondrial translation by the Mitochondrial Translation Optimization Factor 1, MTO1, as a novel player in this scenario. We demonstrate that MTO1 mediates tRNA modification and controls mitochondrial translation rate in a highly tissue-specific manner associated with tissue-specific OXPHOS defects.

Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation.

Post-translational modification of mitochondria as a novel mode of regulation.

Mitochondria not only form the metabolic hub, but also are crucial players in many cellular pathways, like apoptosis and innate immune response, putting the organelle in a central position in controlling cellular function and fate. As novel and powerful regulators of mitochondrial processes and hence mitochondrial-controlled pathways, post-translational modifications (PTMs) have emerged in the last years. In this review, we will summarize the current state of knowledge on PTMs occurring in mammalian mitochondria with a focus on phosphorylation, acetylation, succinylation and ubiquitination.

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action.