A5045351514- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Photosynthetic Processes and Mechanisms
- Metabolism and Genetic Disorders
- Metalloenzymes and iron-sulfur proteins
- Microbial Metabolic Engineering and Bioproduction
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Protein Structure and Dynamics
- Coenzyme Q10 studies and effects
- Enzyme Structure and Function
- Cardiac Ischemia and Reperfusion
- Genomics and Phylogenetic Studies
- Electron Spin Resonance Studies
- Alzheimer's disease research and treatments
- Photoreceptor and optogenetics research
- Nitric Oxide and Endothelin Effects
- Traditional and Medicinal Uses of Annonaceae
- Spectroscopy and Quantum Chemical Studies
- Biochemical Acid Research Studies
- Advanced Proteomics Techniques and Applications
- Anesthesia and Neurotoxicity Research
- Cocoa and Sweet Potato Agronomy
- Redox biology and oxidative stress
University Medical Center
2014-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2019-2023
University of Cologne
2019-2023
Radboud Institute for Molecular Life Sciences
2016-2023
Radboud University Nijmegen
2014-2023
Radboud University Medical Center
2014-2023
Goethe University Frankfurt
2009-2019
Wellcome Centre for Mitochondrial Research
2014
Goethe Institute
2007-2013
Georg Speyer Haus
2012
Cardiolipin stabilized supercomplexes of Saccharomyces cerevisiae respiratory chain complexes III and IV (ubiquinol:cytochrome c oxidoreductase cytochrome oxidase, respectively), but was not essential for their formation in the inner mitochondrial membrane because they were found also a cardiolipin-deficient strain. Reconstitution with cardiolipin largely restored wild-type stability. The putative interface comprises transmembrane helices cytochromes b c1 tightly bound cardiolipin. Subunits...
Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles, and neuron synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APP(sw)PS2(N141I) double-transgenic APP152 mice develop Abeta plaques. Cross-breeding generates triple ((triple)AD) that combine both pathologies one model. To determine functional consequences of the combined pathologies, we performed a proteomic analysis followed validation....
Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated and develop neurofibrillary tangles. The consequences pathology were investigated here by proteomics followed functional analysis. Mainly metabolism-related proteins including mitochondrial respiratory chain complex components, antioxidant enzymes, synaptic identified as modified in proteome pattern mice. Significantly, reduction V levels revealed using was also confirmed...
Proton-pumping complex I of the mitochondrial respiratory chain is among largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated many hereditary degenerative disorders. We report x-ray structure at a resolution 3.6 3.9 angstroms, describing detail central subunits that execute bioenergetic function. A continuous axis basic acidic residues running centrally through arm...
Proton-pumping respiratory complex I is one of the largest and most complicated membrane protein complexes. Its function critical for efficient energy supply in aerobic cells, malfunctions are implicated many neurodegenerative disorders. Here, we report an x-ray crystallographic analysis mitochondrial I. The positions all iron-sulfur clusters relative to arm were determined complete enzyme complex. ubiquinone reduction site resides close 30 angstroms above domain. arrangement functional...
Objective— The enzyme telomerase and its catalytic subunit the reverse transcriptase (TERT) are important for maintenance of telomere length in nucleus. Recent studies provided evidence a mitochondrial localization TERT. Therefore, we investigated exact TERT within mitochondria function. Methods Results— Here, demonstrate that is localized matrix mitochondria. binds to DNA at coding regions ND1 ND2. Binding protects against ethidium bromide–induced damage. increases overall respiratory chain...
Aims: Intracellular amyloid beta (Aβ) oligomers and extracellular Aβ plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, molecular signals triggering production largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) sufficient to increase generation thereby initiate a vicious cycle further impairing mitochondrial function. Results: Complex I III dysfunction was induced cell model using respiratory inhibitors rotenone...
We have analyzed the distribution of mitochondrial contact site and cristae organizing system (MICOS) complex proteins intermembrane space bridging (MIB) over (sub)complexes species. The MICOS are associated with formation maintenance cristae. Indeed, presence genes in genomes correlates well cristae: all containing species at least one gene cristae-less none. Mic10 is most widespread gene, while Mic60 appears be oldest one, as it originates ancestors mitochondria, proteobacteria. In...
Diazoxide and 5‐hydroxydecanoate (5‐HD; C10:0) are reputed to target specifically mitochondrial ATP‐sensitive K + (K ATP ) channels. Here we describe channel‐independent targets of diazoxide 5‐HD in the heart. Using submitochondrial particles isolated from pig heart, found that (10‐100 μ m dose‐dependently decreased succinate oxidation without affecting NADH oxidation. Pinacidil, a non‐selective channel opener, did not inhibit However, it selectively inhibited These direct inhibitory effects...
We showed that the human respiratory chain is organized in supramolecular assemblies of complexes, respirasomes. The mitochondrial complexes I (NADH dehydrogenase) and III (cytochrome c reductase) form a stable core respirasome to which complex IV oxidase) can also bind. An analysis state respirasomes patients with an isolated deficiency single provided evidence formation essential for assembly/stability I, major entry point substrates. Genetic alterations leading loss prevented led...
Vacuolar proton-translocating ATPase (holoATPase and free membrane sector) was isolated from bovine chromaffin granules by blue native polyacrylamide gel electrophoresis. A 5-fold excess of sector over holoenzyme determined in granule membranes. M9.2, a novel extremely hydrophobic 9.2-kDa protein comprising 80 amino acids, detected the sector. It shows sequence structural similarity to Vma21p, yeast required for assembly vacuolar ATPase. second sector-associated (M8-9) identified...