A5080529215- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Metabolomics and Mass Spectrometry Studies
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Microbial Metabolic Engineering and Bioproduction
- Microbial metabolism and enzyme function
- Metabolism and Genetic Disorders
- Ubiquitin and proteasome pathways
- Photosynthetic Processes and Mechanisms
- Microtubule and mitosis dynamics
- Fluorine in Organic Chemistry
- 14-3-3 protein interactions
University of Freiburg
2017-2024
La Trobe University
2015
Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control have been linked to various diseases. Different views exist on the composition of human mitochondrial proteome. We classified >8,000 proteins in preparations cells defined a high-confidence proteome >1,100 (MitoCoP). identified interactors translocases, respiratory chain, ATP synthase assembly factors. The abundance MitoCoP covers six orders magnitude amounts 7% with chaperones HSP60-HSP10...
The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion β-barrel proteins into outer membranes. Homologous Omp85 are essential for membrane precursors. It is unknown if precursors threaded through Omp85-channel interior exit laterally or they translocated at Omp85-lipid interface. We have mapped interaction a precursor in transit with mitochondrial Sam50 native environment. channel interior, interacts an internal loop, inserts lateral gate by β-signal...
The exchange of metabolites between the mitochondrial matrix and cytosol depends on β-barrel channels in outer membrane α-helical carrier proteins inner membrane. essential translocase (TIM) chaperones escort these through intermembrane space, but structural mechanistic details remain elusive. We have used an integrated biology approach to reveal functional principle TIM chaperones. Multiple clamp-like binding sites hold a translocation-competent elongated form, thus mimicking...
Biogenesis of complex IV the mitochondrial respiratory chain requires assembly factors for subunit maturation, co-factor attachment and stabilization intermediate assemblies. A pathogenic mutation in COA6, leading to substitution a conserved tryptophan cysteine residue, results loss activity cardiomyopathy. Here, we demonstrate that defect correlates with severe patient heart but not fibroblasts. Complete COA6 using gene editing HEK293T cells resulted profound growth due deficiency, caused...
Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in metabolite pools subcellular compartments. Thus, mutations affecting mitochondrial energy metabolism could cause metabolic alterations mitochondria compared cytoplasm. Given that pool cytosol is larger than of other compartments, profiling total miss these compartment-specific alterations.To reveal differences, and cytoplasmic fraction baker's yeast Saccharomyces...
Mutations in mitochondrial membrane proteins could cause physiological and metabolic alterations mitochondria as well cytosol. In order to address the origin of these alterations, cytosol yeast wild-type BY4741 two mutants, sdh2Δ atp4Δ, were isolated from whole cells. These three compartments, namely mitochondria, cell, analyzed by gas chromatography-mass spectrometry based profiling, identifying seventy-three metabolites altogether, which sixteen or ten not detected either...
SYM1 is an ortholog of the human MPV17 gene whose mutation causes mitochondrial DNA depletion syndrome. Sym1 protein located in inner membrane and its deletion results impaired bioenergetic functions morphological features under stress conditions. However, both Mpv17 have not been clearly characterized. Recently, compartment-specific metabolic alterations to mutations or inhibitors were revealed by analyzing isolated mitochondria. This development opens new doors for uncovering function...