A5049988427- Mitochondrial Function and Pathology
- Nitric Oxide and Endothelin Effects
- ATP Synthase and ATPases Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Metabolism and Genetic Disorders
- Amyotrophic Lateral Sclerosis Research
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Photosynthetic Processes and Mechanisms
- Inflammatory mediators and NSAID effects
- Advanced Proteomics Techniques and Applications
- Advanced Nanomaterials in Catalysis
- Cancer-related molecular mechanisms research
- Cardiac Ischemia and Reperfusion
- Circular RNAs in diseases
- Autophagy in Disease and Therapy
- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Cell death mechanisms and regulation
Goethe University Frankfurt
2013-2024
German Centre for Cardiovascular Research
2016-2020
University Hospital Frankfurt
2011-2016
Ludwig-Maximilians-Universität München
2016
Max Planck Institute for Heart and Lung Research
2011
Martin Luther University Halle-Wittenberg
2006
The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important lncRNAs.Epigenetically controlled lncRNAs in human umbilical vein were searched exon-array analysis after knockdown histone demethylase JARID1B. Molecular mechanisms investigated RNA pulldown immunoprecipitation, mass spectrometry, microarray, several approaches, CRISPR-Cas9, assay for...
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was first to be genetically defined by a point mutation in DNA (mtDNA). A molecular diagnosis achieved up 95% of cases, vast majority which are accounted for 3 mutations within complex I subunit–encoding genes mtDNA (mtLHON). Here, we resolve enigma LHON absence pathogenic mutations. We describe biallelic nuclear encoded gene, DNAJC30, 33 unsolved patients from 29 families establish an autosomal...
Regulation of the turnover complex I (CI), largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and assembly. Here, we report that NADH-oxidizing N-module CI is turned over at a higher rate largely independently rest by matrix protease ClpXP, which selectively removes degrades damaged subunits. The observed mechanism seems to be safeguard against accumulation dysfunctional arising from inactivation subunits due attrition...
In vascular endothelial cells, cysteine metabolism by the cystathionine γ lyase (CSE), generates hydrogen sulfide-related sulfane sulfur compounds (H2Sn), that exert their biological actions via S-sulfhydration of target proteins. This study set out to map "S-sulfhydrome" (ie, spectrum proteins targeted H2Sn) in human cells.Liquid chromatography with tandem mass spectrometry was used identify S-sulfhydrated cysteines cell and β3 integrin intraprotein disulfide bond rearrangement. Functional...
Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable regrowth they often fail to re-innervate target tissues. Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that accelerates axonal regrowth, restoration neuromuscular synapses recovery sensory functions after the sciatic nerve. Oppositely, deficient have long-lasting in function tests due enhanced losses neurons stronger...
Plants and many lower organisms, but not mammals, express alternative oxidases (AOX) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when classical chain is impaired, limiting excess production of radicals supporting redox metabolic homeostasis. AOX Ciona intestinalis has been used study mitigate impairments in mammalian cell-lines, Drosophila disease models...
Secondary mitochondrial dysfunction is a feature in wide variety of human protein aggregate diseases caused by mutations different proteins, both the central nervous system and striated muscle. The functional relationship between expression mutated largely unknown. In particular, mechanism how this drives disease process still elusive. To address issue for myopathies, we performed comprehensive, multi-level analysis pathology skeletal muscles patients with intermediate filament desmin...
Leigh syndrome is one of the most common neurological phenotypes observed in pediatric mitochondrial disease presentations. It characterized by symmetrical lesions found on neuroimaging basal ganglia, thalamus, and brainstem a loss motor skills delayed developmental milestones. Genetic diagnosis complicated account vast genetic heterogeneity with >75 candidate disease-associated genes having been reported to date. Candidate are still emerging, being identified when "omics" tools (genomics,...
Neuropathic pain is a chronic debilitating disease that often unresponsive to currently available treatments. Emerging lines of evidence indicate reactive oxygen species (ROS) are required for the development and maintenance neuropathic pain. However, little known about endogenous mechanisms neutralize pain-relevant effects ROS. In present study, we tested whether stress-responsive antioxidant protein Sestrin 2 (Sesn2) blocks ROS-induced processing in vivo.We observed Sesn2 mRNA expression...
Electron transfer from all respiratory chain dehydrogenases of the electron transport (ETC) converges at level quinone (Q) pool. The Q redox state is thus a function input (reduction) and output (oxidation) closely reflects mitochondrial state. Disruption flux cytochrome bc1 complex (cIII) or c oxidase (cIV) shifts poise to more reduced which generally sensed as stress. To cope with stress, many species, but not insects vertebrates, express alternative (AOX) acts an sink for by-passes cIII...
The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPKα1 catalytic subunit has been implicated in angiogenesis, little known about role played AMPKα2 vascular repair.To determine of repair.Recovery blood flow after femoral artery ligation was impaired (>80%) AMPKα2-/- versus wild-type mice, a phenotype reproduced mice lacking myeloid cells (AMPKα2ΔMC). Three days ligation, neutrophil infiltration into ischemic limbs AMPKα2ΔMC lower than that despite being...
Significance The stereotype of ROS produced by NADPH oxidases as cause malignant diseases persists in a generalized manner. In fact, high levels formation could be harmful the context disease process. This study demonstrates that loss oxidase Nox4, constitutive source ROS, promotes cancerogen-induced solid tumors. Accordingly, certain tonic, low level Nox4-derived hydrogen peroxide appears to reduce risk tumor formation.
Upregulations of neuronal nitric oxide synthase (nNOS) in the rodent brain have been associated with aging. To address underlying mechanisms we generated SH-SY5Y cells constitutively expressing nNOS at a level similar to mouse (nNOS+ versus MOCK). Initial experiments revealed S-nitrosylations (SNO) key players protein homeostasis: heat shock cognate HSC70/HSPA8 within its nucleotide-binding site, and UBE2D ubiquitin conjugating enzymes catalytic site cysteine. HSPA8 is involved folding,...
Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), cerebrovascular condition with occlusive lesions and compensatory angiogenesis. Mysterin mutations, together exposure to environmental trigger factors, lead an elevated stroke risk since childhood. induced during cell stress, function as cytosolic AAA+ ATPase ubiquitylation enzyme. Little knowledge exists, in context mysterin needed. Here, we found that genetic ablation of several...
Leigh syndrome is a progressive neurodegenerative disorder, most commonly observed in paediatric mitochondrial disease, and often associated with pathogenic variants complex I structural subunits or assembly factors resulting isolated respiratory chain deficiency. Clinical heterogeneity has been reported, but key diagnostic findings are developmental regression, elevated lactate characteristic neuroimaging abnormalities. Here, we describe three affected children from two unrelated families...
Increased levels of low-density lipoproteins are well-established risk factors endothelial dysfunction and the metabolic syndrome. In this study, we evaluated effect native lipoprotein (nLDL) oxidized LDL (oxLDL) on expression genes renin-angiotensin system (angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT1) their receptors (low-density receptor: LDLR; lectin-like oxLDL LOX-1; toll-like receptor 4: TLR4) in primary cultures human umbilical vein cells. ACE AT1...
In eukaryotic cells, maintenance of cellular ATP stores depends mainly on mitochondrial oxidative phosphorylation (OXPHOS), which in turn requires sufficient oxygenation. The crucial role proper oxygenation for viability is reflected by involvement several mechanisms, sense hypoxia and regulate activities respiratory complexes according to available oxygen concentrations. Here, we focus mouse nitric oxide-associated protein 1 (mNOA1), has been identified as an important component the...