A5045020040- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Transplantation: Methods and Outcomes
- Analytical Chemistry and Chromatography
- Mass Spectrometry Techniques and Applications
- Animal Genetics and Reproduction
- Glycosylation and Glycoproteins Research
- Dialysis and Renal Disease Management
- ATP Synthase and ATPases Research
- HIV-related health complications and treatments
- Organ Transplantation Techniques and Outcomes
- Mast cells and histamine
- Lipoproteins and Cardiovascular Health
- CRISPR and Genetic Engineering
- Renal Transplantation Outcomes and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Diabetes, Cardiovascular Risks, and Lipoproteins
- PARP inhibition in cancer therapy
- Virus-based gene therapy research
- Genetic Mapping and Diversity in Plants and Animals
- Adenosine and Purinergic Signaling
Innsbruck Medical University
2018-2024
Universität Innsbruck
2018-2024
Johannes Gutenberg University Mainz
2004
Significance Cardiolipins are a unique class of phospholipids in mitochondrial membranes that crucial for cellular bioenergetics as they stabilize respiratory chain complexes. In contrast to most other phospholipids, cardiolipins substituted with four, rather than only two fatty acyl side chains. Consequently, this opens up vast number different theoretically possible molecular lipid species. Experimentally assessing the diversity cardiolipin species is analytically challenging. study we...
Significance Although sequencing of the human genome was completed years ago, we still do not know about physiological significance thousands predicted proteins, particularly membrane proteins. On other hand, for approximately 100 enzymes, no coding gene is known even though their enzymatic reaction has been well characterized. In this work, assign one those proteins (transmembrane protein 189; TMEM189) to reactions with an uncharacterized (plasmanylethanolamine desaturase). This enzyme...
Cardiolipin (CL) is a phospholipid specific for mitochondrial membranes and crucial many core tasks of this organelle. Its acyl chain configurations are tissue specific, functionally important, generated via post-biosynthetic remodeling. However, process lacks the necessary specificity to explain CL diversity, which especially evident highly compositions in mammalian tissues. To investigate so far elusive regulatory origin homeostasis mice, we combine lipidomics, integrative transcriptomics,...
Deficient ether lipid biosynthesis in rhizomelic chondrodysplasia punctata and other disorders is associated with a wide range of severe symptoms including small stature proximal shortening the limbs, contractures, facial dysmorphism, congenital cataracts, ichthyosis, spasticity, microcephaly, mental disability. Mouse models are available but show less symptoms. In both humans mice, it has remained elusive which can be attributed to lack plasmanyl or plasmenyl lipids. The latter compounds,...
The molecular assembly of cells depends not only on the balance between anabolism and catabolism but to a large degree building blocks available in environment. For cultured mammalian cells, this is largely determined by composition applied growth medium. Here, we study impact lipids medium mitochondrial membrane architecture function combining LC-MS/MS lipidomics functional tests with lipid supplementation experiments an otherwise serum-free lipid-free cell culture model. We demonstrate...
Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the bond, PEDS1 exclusively synthesizes a specific subclass lipids, plasmalogens, introducing vinyl double bond into phospholipids. Ether characterized an linkage at sn-1 position glycerol backbone they found membranes different cell types. Decreased plasmalogen levels have been associated with...
Deficiency of the transacylase tafazzin due to loss function variants in X-chromosomal TAFAZZIN gene causes Barth syndrome (BTHS) with severe neonatal or infantile cardiomyopathy, neutropenia, myopathy, and short stature. The condition is characterized by drastic changes composition cardiolipins, a mitochondria-specific class phospholipids. Studies examining impact deficiency on metabolism other phospholipids have so far generated inhomogeneous partly conflicting results. Recent studies...
Genome editing in mice using either classical approaches like homologous recombination or CRISPR/Cas9 has been reported to harbor off target effects (insertion/deletion, frame shifts gene segment duplications) that lead mutations not only close proximity the site but also outside. Only genomes of few engineered mouse strains have sequenced. Since role ether-lipid cleaving enzyme alkylglycerol monooxygenase (AGMO) physiology and pathophysiology remains enigmatic, we created a knockout model...
Plasmalogens are an abundant class of glycerophospholipids in the mammalian body, with special occurrence brain and immune cell membranes. Plasmanylethanolamine desaturase (PEDS1) is final enzyme plasmalogen biosynthesis, which introduces characteristic 1-O-alk-1'-enyl double bond. The recent sequence identification PEDS1 as transmembrane protein 189 showed that its related to a plant desaturases (FAD4), whom it shares motif 8 conserved histidines, essential for enzymatic activity. In...
Abstract The molecular assembly of cells depends not only on their balance between anabolism and catabolism, but to a large degree also the building blocks available in environment. For cultivated mammalian cells, this is largely determined by composition growth medium used. Here we study impact lipids mitochondrial membrane architecture function combining LC-MS/MS lipidomics functional tests with lipid supplementation experiments an otherwise serum- lipid-free cell culture model. We...
Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), only enzyme capable cleaving 1-O-alkyl ether bond lipids. Expression and enzymatic activity this can be detected in a variety tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as cofactor, mice with reduced levels have alterations body fat distribution blood lipid concentrations. In addition, manipulation AGMO macrophages led to significant changes...
<title>Abstract</title> Administration of tetrahydrobiopterin (BH4) has been shown to attenuate acute allograft rejection in a murine heart transplantation model manner similar that cyclosporine A. However, its mechanism action on immune cells remains largely unknown. A fully MHC-mismatched (C3H/He C57BL/6) mouse transplant was used this study. The recipients were treated with BH4 or Cyclosporine six days. degree assessed by histopathological analysis, splenocytes analyzed flow cytometry,...
Abstract Trapped Ion Mobility Spectrometry (TIMS) has demonstrated promissing potential as a powerful discriminating method when coupled with mass spectrometry, enhancing the precision of feature annotation. Such technique is particularly valuable for lipids, where large number isobaric but structurally distinct molecular species often coexist within same sample matrix. In this study we explored ion mobility ether lipid isomer differentiation. Mammalian phospholipids are characterized by...
Introduction: Phospholipid transfer protein (PLTP) is mainly involved in high-density lipoprotein (HDL) metabolism. The role of PLTP atherogenesis still controversial. We aimed to investigate activity hemodialysis (HD) patients, a population which has an increased risk for the development atherosclerosis. Methods: and other markers were analyzed blood samples from 68 HD patients matched group healthy controls. Results: Serum was nearly doubled comparison controls (median 43.0 vs. 22.4...
DRA (down regulated in adenoma) ist ein intestinaler Anionenaustauscher mit einem C-terminalen PDZ-Interaktionsmotiv (ETKF). Diese Sequenz vermittelt vitro die Interaktion den PDZ-Adapterproteinen E3KARP, EBP50 und PDZK1 sowie eventuell CAL. Die funktionelle Bedeutung dieser nicht bekannt. Anhand der anderer Membrantransporter scheint Einfluss auf Regulation und/oder Expression Plasmamembran möglich. Ziel: Entwicklung eines Systems für Coexpression von (konstitutiv) verschiedenen...
Abstract Deficient ether lipid biosynthesis in rhizomelic chondrodysplasia punctata and other disorders is associated with a wide range of severe symptoms including small stature proximal shortening the limbs, contractures, facial dysmorphism, congenital cataracts, ichthyosis, spasticity, microcephaly, mental disability. Mouse models are available but show less symptoms. In both humans mice it has remained elusive which can be attributed to lack plasmanyl or plasmenyl lipids. The latter...