A5050083499- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- Protist diversity and phylogeny
- ATP Synthase and ATPases Research
- Photoreceptor and optogenetics research
- Hedgehog Signaling Pathway Studies
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Renal and related cancers
- Biotin and Related Studies
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Fetal and Pediatric Neurological Disorders
- Enzyme Structure and Function
- Click Chemistry and Applications
- Cystic Fibrosis Research Advances
- Glycosylation and Glycoproteins Research
- Biosensors and Analytical Detection
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Genetic Syndromes and Imprinting
- 14-3-3 protein interactions
- Electrochemical sensors and biosensors
Saarland University
2019-2025
University of Göttingen
2010-2016
Universitätsmedizin Göttingen
2013-2016
Stanford University
2015
University of Freiburg
2005-2011
Institute of Molecular Biotechnology
2010
La Trobe University
2006
Osnabrück University
2006
Centre de Génétique Moléculaire
2006
Centre National de la Recherche Scientifique
2006
The Saccharomyces cerevisiae Taz1 protein is the orthologue of human Tafazzin, a that when inactive causes Barth Syndrome (BTHS), severe inherited X-linked disease. mitochondrial acyltransferase involved in remodeling cardiolipin. We show an outer membrane exposed to intermembrane space (IMS). Transport into mitochondria depends on receptor Tom5 translocase (TOM complex) and small Tim proteins IMS, but independent sorting assembly complex (SAM). TAZ1 deletion yeast leads growth defects...
Transport of metabolites across the mitochondrial inner membrane is highly selective, thereby maintaining electrochemical proton gradient that functions as main driving force for cellular adenosine triphosphate synthesis. Mitochondria import many preproteins via presequence translocase membrane. However, reconstituted Tim23 protein constitutes a pore remaining mainly in its open form, state would be deleterious organello. We found intermembrane space domain Tim50 induced channel to close....
The primary cilium is a signaling compartment that interprets Hedgehog signals through changes of its protein, lipid, and second messenger compositions. Here, we combine proximity labeling cilia with quantitative mass spectrometry to unbiasedly profile the time-dependent alterations ciliary proteome in response Hedgehog. This approach correctly identifies three factors known undergo Hedgehog-regulated redistribution reveals two such additional proteins. First, find regulatory subunit...
Saccharomyces cerevisiae Mdm38 and Ylh47 are homologues of human Letm1, a protein implicated in Wolf-Hirschhorn syndrome. We analyzed the function yeast mitochondria to gain insight into role Letm1. find that mdm38Delta have reduced amounts certain mitochondrially encoded proteins low levels complex III IV accumulate unassembled Atp6 V respiratory chain. is especially required for efficient transport cytochrome b across inner membrane, whereas plays minor this process. Both form stable...
Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase outer membrane (TOM) associates with presequence inner (TIM23) in a supercomplex. Different views exist on mechanism how TIM23 mediates preprotein sorting to either matrix or membrane. On one hand, two forms were proposed, transport form containing translocase-associated motor (PAM; TIM23-PAM) and Tim21 (TIM23(SORT)). other it was reported that PAM are permanently associated...
Regulation of eukaryotic cytochrome oxidase assembly occurs at the level Cox1 translation, its central mitochondria-encoded subunit. Translation COX1 messenger RNA is coupled to complex in a negative feedback loop: translational activator Mss51 thought be sequestered intermediates, rendering it incompetent promote translation. In this study, we identify Coa3 (cytochrome factor 3; Yjl062w-A), novel regulator mitochondrial translation and assembly. We show that Cox14 form intermediates with...
The primary cilium constitutes an organelle that orchestrates signal transduction independently from the cell body. Dysregulation of this intricate molecular architecture leads to severe human diseases, commonly referred as ciliopathies. However, underpinnings how ciliary signaling a specific cellular output remain elusive. By combining spatially resolved optogenetics with RNA sequencing and imaging, we reveal novel cAMP signalosome is functionally distinct cytoplasm. We identify genes...
Cox1, the core subunit of cytochrome c oxidase, receives two heme a cofactors during assembly 13-subunit enzyme complex. However, at which step process and how is inserted into Cox1 have remained an enigma. Shy1, yeast SURF1 homolog, has been implicated in transfer to whereas synthase, Cox15, catalyzes final synthesis. Here we performed comprehensive analysis oxidase intermediates containing Shy1. Our analyses suggest that Cox15 displays role assembly, independent its functions as synthase....
Compartmentalization of cellular signaling forms the molecular basis behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary has been challenging due to lack tools investigate signaling. Here, we describe nanobody-based targeting approach for optogenetic in mammalian cells and vivo zebrafish specifically analyze function. Thereby,...
Biogenesis of respiratory chain complexes depends on the expression mitochondrial-encoded subunits. Their synthesis occurs membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in mitochondrial translation products are among major causes disorders. Mdm38 related Letm1, a protein affected Wolf-Hirschhorn syndrome patients. Like Mba1 Oxa1, an inner that interacts with involved biogenesis. We find simultaneous loss severe synthetic defects biogenesis...
Mitochondrial ribosomes synthesize core subunits of the inner membrane respiratory chain complexes. In mitochondria, translation is regulated by mRNA-specific activator proteins and occurs on membrane-associated ribosomes. Mdm38/Letm1 a conserved receptor for mitochondrial specifically involved in biogenesis. addition, Mdm38 its higher eukaryotic homolog Letm1, function as K(+)/H(+) or Ca(2+)/H(+) antiporters membrane. Here, we identify ribosome-binding domain (RBD) determine crystal...
Ascorbate peroxidase (APEX) is a versatile labeling enzyme used for live-cell proteomics at high spatial and temporal resolution. However, toxicity of its substrate hydrogen peroxide background by endogenous peroxidases limit use to in vitro studies specific cell types. By combining APEX2 with D-amino acid oxidase locally produce peroxide, we establish more versatile, improved APEX (iAPEX) workflow that minimizes reduces non-specific labeling. We employ iAPEX perform cellular microdomain,...
Primary cilia are hair-like sensory organelles that project from the cell bodies of most types, including appetite-regulatory hypothalamic neurons where they likely help sense metabolic factors to regulate food intake. We hypothesized characterising proteins present in primary would shed mechanistic insights into their role and identify new therapeutic targets for obesity. therefore targeted ascorbate peroxidase APEX2 human induced pluripotent stem cells (hiPSC)-derived biotinylate ciliary...
Defects in mitochondrial energy metabolism lead to severe human disorders, mainly affecting tissues especially dependent on oxidative phosphorylation, such as muscle and brain. Leigh Syndrome describes a encephalomyopathy infancy, frequently caused by mutations SURF1 . SURF1, termed Shy1 Saccharomyces cerevisiae , is conserved assembly factor for the terminal enzyme of respiratory chain, cytochrome c oxidase. Although molecular function SURF1/Shy1 still enigmatic, loss leads oxidase...