A5026603384- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Antifungal resistance and susceptibility
- Photosynthetic Processes and Mechanisms
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Advanced Fluorescence Microscopy Techniques
- Parasitic Diseases Research and Treatment
- Extracellular vesicles in disease
- Hereditary Neurological Disorders
- Cancer Immunotherapy and Biomarkers
- Polysaccharides and Plant Cell Walls
- Connective tissue disorders research
- Genetic Neurodegenerative Diseases
- Cancer-related Molecular Pathways
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Skin and Cellular Biology Research
- Autophagy in Disease and Therapy
- Lipid metabolism and biosynthesis
- Botulinum Toxin and Related Neurological Disorders
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2015-2024
University of Cologne
2014-2024
University Hospital Cologne
2019-2020
National Imaging Facility
2018
University of Ottawa
2007-2010
Max Planck Institute for Biophysical Chemistry
2003-2006
Max Planck Society
2003-2005
Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage YME1L OMA1 at two distinct sites leads to accumulation of both long short forms maintains mitochondrial fusion. Stress-induced processing converts completely into isoforms, inhibits fusion, triggers fragmentation. Here, we have analyzed function different in cells lacking YME1L, OMA1, or both. Unexpectedly, deletion Oma1 restored...
The expanding field of extracellular vesicle (EV) research needs reproducible and accurate methods to characterize single EVs. Nanoparticle Tracking Analysis (NTA) is commonly used determine EV concentration diameter. As the lacking easily confirm validate NTA data, questioning reliability measurements remains highly important. In this regard, a comparison addressing measurement quality between different devices such as Malvern's NanoSight NS300 or Particle Metrix' ZetaView has not yet been...
The surface protein composition of extracellular vesicles (EVs) is related to the originating cell and may play a role in vesicle function. Knowledge content individual EVs still limited because technical challenges analyse small vesicles. Here, we introduce novel multiplex bead-based platform investigate up 39 different markers one sample. combination capture antibody beads with fluorescently labelled detection antibodies allows analysis that carry recognized by both antibodies. This new...
The size of endocytic clathrin-coated vesicles (CCVs) is remarkably uniform, suggesting that it optimized to achieve the appropriate levels cargo and lipid internalization. three most abundant proteins in mammalian CCVs are clathrin two cargo-selecting, adaptors, CALM AP2. Here we demonstrate depletion causes a substantial increase ratio "open" pits (CCPs) "necked"/"closed" doubling CCP/CCV diameter, whereas AP2 has opposite effects. Depletion either adaptor, however, significantly inhibits...
Generation of a barrier in multi-layered epithelia like the epidermis requires restricted positioning functional tight junctions (TJ) to most suprabasal viable layer. This necessitates tissue-level polarization and cytoskeleton through unknown mechanisms. Using quantitative whole-mount imaging, genetic ablation, traction force microscopy atomic microscopy, we find that ubiquitously localized E-cadherin coordinates tissue tension-bearing adherens junction (AJ) F-actin organization allow...
Mitochondria are dynamic organelles that undergo regulated fission and fusion events essential to maintain metabolic stability. We previously demonstrated the mitochondrial GTPase DRP1 is a substrate for SUMOylation. To further understand how SUMOylation impacts function, we searched SUMO protease may affect dynamics. demonstrate cytosolic pool of SENP5 catalyzes cleavage SUMO1 from number substrates. Overexpression rescues SUMO1-induced fragmentation partly due downregulation DRP1. By...
c-Jun N-terminal kinase (JNK) 1-dependent signaling plays a crucial role in the development of obesity-associated insulin resistance. Here we demonstrate that JNK activation not only occurs peripheral tissues, but also hypothalamus and pituitary obese mice. To resolve importance JNK1 hypothalamic/pituitary circuitry, have generated mice with conditional inactivation nestin-expressing cells (JNK1 ΔNES mice). exhibit improved sensitivity both CNS glucose metabolism, as well protection from...
The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity cancer. Here, we characterize T-cell subsets expression immune checkpoint molecules in head neck squamous cell carcinoma (HNSCC). We analyzed TIL primary tumors (n = 34), blood (peripheral mononuclear cells (PBMC); n 34) non-cancerous mucosa 7) 34 treatment-naïve HNSCC patients PBMC 15 healthy controls. Flow cytometry analyses revealed a highly variable infiltration mainly an effector memory phenotype...
Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity lower limbs, owing to progressive retrograde degeneration long corticospinal axons. Spastin a conserved microtubule (MT)-severing protein, involved processes requiring rearrangement cytoskeleton concert membrane remodeling, such as neurite branching, axonal growth, midbody abscission, endosome tubulation. Two isoforms...
Understanding the mechanisms governing selective turnover of mutation-bearing mtDNA is fundamental to design therapeutic strategies against diseases. Here, we show that specific damage leads an exacerbated turnover, independent canonical macroautophagy, but relying on lysosomal function and ATG5. Using proximity labeling Twinkle as a nucleoid marker, demonstrate induces membrane remodeling endosomal recruitment in close mitochondrial sub-compartments. Targeting nucleoids controlled by...
Integration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration uniquely contribute to function, immature are endowed with critical period heightened plasticity, yet it remains unclear which mechanisms sustain this form plasticity during neuronal maturation. We found that as enter their period, transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies dendrites fuel plasticity....
Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues can dynamically change in response to different conditions. Although the transcriptional programs govern biogenesis respiratory function well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates expression of a...
Dynamin-related GTPase proteins (DRPs) are main players in membrane remodelling. Conserved DRPs called mitofusins (Mfn1/Mfn2/Fzo1) mediate the fusion of mitochondrial outer membranes (OM). OM depends on self-assembly and activity as well two other proteins, Ugo1 Mdm30. Here, we define distinct steps cycle using vitro vivo approaches. We demonstrate that yeast Fzo1 assembles into homo-dimers, depending GTP binding to Fzo1. homo-dimers further associate upon formation contacts, allowing...
Significance In the human organism, guanylate-binding proteins (GBPs) are involved in antimicrobial and antiviral activity, but mechanism of GBPs’ action remains poorly understood. We have discovered that binding a substrate molecule, GTP, to enzyme triggers release an aforemasked lipid anchor, which results GBP polymerization on one hand attachment GBPs membranes other. Thus, membrane competes with protein and, furthermore, leads tethering, could play role clearance engulfed pathogens from...
The mitochondrial compartment of budding yeast (Saccharomyces cerevisiae) is a highly dynamic net-like structure tubules that constantly undergo fusion and fission. outer membrane protein Fis1p plays crucial role in Here we report on the temporal spatial dynamics this organelle wild-type cells fis1Δ mutants. Mitochondria mutants adapt their network to change carbon source. We find frequencies apparent matrix separation events decrease both lacking upon glucose repression. Matrix could be...
Abstract In Arabidopsis (Arabidopsis thaliana), root hairs are formed in cell files over the cleft of underlying cortex cells. This pattern is established by a well-known gene regulatory network transcription factors. this study, we show that WRKY75 suppresses hair development nonroot and it represses expression TRIPTYCHON CAPRICE. The protein binds to CAPRICE promoter yeast one-hybrid assay. Binding fragment requires an intact WRKY protein-binding motif, W box. A comparison spatial...
Remarkable efficacy of immune checkpoint inhibition has been reported for several types solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology checkpoints is essential clinical translational evaluation these drugs. This study a comprehensive analysis cytotoxic T lymphocyte associated molecule 4 (CTLA-4) programmed death 1 ligand (PD-L1) expression adenocarcinoma. PD-L1 CTLA-4 were stained on tumor sections 127 Caucasian patients...
Mitochondrial dysfunction is critically involved in Parkinson's disease, characterized by loss of dopaminergic neurons (DaNs) the substantia nigra (SNc), whereas DaNs neighboring ventral tegmental area (VTA) are much less affected. In contrast to VTA, SNc engage calcium channels generate action potentials, which lead oxidant stress yet unknown pathways. To determine molecular mechanisms linking load with selective cell death presence mitochondrial deficiency, we analyzed redox state and...
The mitochondrial division machinery consists of the large dynamin-related protein Dnm1p (Drp1/Dlp1 in humans), and Fis1p, Mdv1p Caf4p. Proper assembly complexes on surface is crucial for balanced fission fusion events. Using quantitative confocal microscopy, we show that Caf4p important recruitment to mitochondria. assemblies can be divided into at least two morphologically distinguishable fractions. A small subset these appear present as Dnm1p-spirals (or rings) encircle tubule...
Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model disorders linked to mitochondrial dysfunction. While some cases, this effect seems be clearly associated with boosting function, additional alterations as well tissue- cell-type-specific effects might play an important role. We initiated comprehensive analysis the potential PGC-1α-activating drugs pharmaceutically targeted PPAR (bezafibrate, rosiglitazone), AMPK (AICAR,...