A5061217274- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- FOXO transcription factor regulation
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Endometriosis Research and Treatment
- Reproductive Physiology in Livestock
- Bladder and Urothelial Cancer Treatments
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- GDF15 and Related Biomarkers
- Molecular Biology Techniques and Applications
- Liver Disease Diagnosis and Treatment
- Biochemical effects in animals
- Monoclonal and Polyclonal Antibodies Research
- Skin and Cellular Biology Research
- Metabolism, Diabetes, and Cancer
- Pain Mechanisms and Treatments
University of Cologne
2007-2024
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2008-2024
Takeda (United States)
2024
Salk Institute for Biological Studies
2012-2016
Howard Hughes Medical Institute
2012-2016
University of California, Berkeley
2015-2016
Institute on Aging
2016
Torrey Pines Institute For Molecular Studies
2014
Institute of Genetics
2007
Prohibitins comprise an evolutionarily conserved and ubiquitously expressed family of membrane proteins with poorly described functions. Large assemblies PHB1 PHB2 subunits are localized in the inner mitochondria, but various roles other cellular compartments have also been proposed for both proteins. Here, we used conditional gene targeting murine Phb2 to define activities prohibitins. Our experiments restrict function prohibitins mitochondria identify processing dynamin-like GTPase OPA1,...
Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fission, maintained processing the dynamin-like guanosine triphosphatase OPA1 peptidases YME1L OMA1. Cardiac-specific ablation Yme1l in mice activated OMA1 accelerated proteolysis, which triggered fragmentation altered cardiac metabolism. This caused dilated cardiomyopathy heart failure. Cardiac were rescued Oma1 deletion, prevented...
Fusion and fission of mitochondria maintain the functional integrity protect against neurodegeneration, but how mitochondrial dysfunctions trigger neuronal loss remains ill-defined. Prohibitins form large ring complexes in inner membrane that are composed PHB1 PHB2 subunits thought to function as scaffolds. In Caenorhabditis elegans, prohibitin genes affect aging by moderating fat metabolism energy production. Knockdown experiments mammalian cells link prohibitins fusion, they were found...
Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondrial morphology under stress and disease. Stress-induced processing by OMA1 triggersmitochondrial fragmentation, which associated with mitophagy apoptosis vitro. Here, we identify critical regulator neuronal survival vivo demonstrate stress-induced promotes death neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds...
To evaluate safety and mechanism of action mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE).
Prohibitins are highly conserved proteins mainly implicated in the maintenance of mitochondrial function and architecture. Their dysfunctions associated with aging, cancer, obesity, inflammation. However, their possible role pancreatic β-cells remains unknown. The current study documents expression prohibitins human rodent islets key for β-cell survival. Ablation Phb2 mouse sequentially resulted impairment insulin secretion, loss β-cells, progressive alteration glucose homeostasis, and,...
Abstract Mitochondrial dysfunction and alterations in energy metabolism have been implicated a variety of human diseases. fusion is essential for maintenance mitochondrial function requires the prohibitin ring complex subunit prohibitin‐2 (PHB2) at inner membrane. Here, we provide link between PHB2 deficiency hyperactive insulin/IGF‐1 signaling. Deletion podocytes mice, terminally differentiated cells kidney filtration barrier, caused progressive proteinuria, failure, death animals resulted...
B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-κB (NF-κB), BAFF-, and receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing from surface to nucleus. We describe a novel mouse strain that expresses solely excessively naturally occurring splice variant CYLD (CYLDex7/8 mice), which deubiquitinating enzyme integral NF-κB This shorter protein lacks TRAF2 NEMO binding sites present...
Tissue stem cells and germ line or embryonic were shown to have reduced oxidative metabolism, which was proposed be an adaptive mechanism reduce damage accumulation caused by reactive oxygen species. However, alternate explanation is that are less dependent on specialized cytoplasmic functions compared with differentiated cells, therefore, having a high nuclear-to-cytoplasmic volume ratio consequently low mitochondrial content. To determine whether rely not respiration, we selectively...
Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, key node the proteostasis network. FOXO4, insulin/IGF-1 responsive transcription factor, regulates proteasome activity hESCs. We find that loss FOXO4 reduces potential hESCs to differentiate into neural lineages. Therefore, crosses evolutionary boundaries links invertebrate...
Although anti-tumor activities of type I interferons (IFNs) have been recognized for decades, the molecular mechanisms contributing to clinical response remain poorly understood. The complex functions these pleiotropic cytokines include stimulation innate and adaptive immune responses against tumors as well direct inhibition tumor cells. In high-grade, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, nadofaragene firadenovec, a non-replicating adenovirus...