A5004797505- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- Lipid metabolism and biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Microbial Metabolic Engineering and Bioproduction
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- RNA modifications and cancer
- Studies on Chitinases and Chitosanases
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- Heat shock proteins research
- HIV Research and Treatment
- Protist diversity and phylogeny
- Genomic variations and chromosomal abnormalities
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Yersinia bacterium, plague, ectoparasites research
- Bacterial Genetics and Biotechnology
University of Tübingen
2014-2025
Veneto Institute of Molecular Medicine
2006-2010
Dulbecco Telethon Institute
2006-2010
Ludwig-Maximilians-Universität München
2002-2005
The understanding of the processes underlying organellar function and inheritance requires identification characterization molecular components involved. We pursued a genomic approach to define complements genes required for respiratory growth mitochondria with normal morphology in yeast. With systematic screening deletion mutant library covering nonessential Saccharomyces cerevisiae numbers known be establishment wild-type-like mitochondrial structure have been more than doubled. In...
Wolf -Hirschhorn syndrome (WHS) is a complex congenital caused by monoallelic deletion of the short arm chromosome 4. Seizures in WHS have been associated with LETM1 gene.LETM1 encodes for human homologue yeast Mdm38p, mitochondria-shaping protein unclear function.Here we show that located inner membrane, exposed to matrix and oligomerized higher molecular weight complexes unknown composition.Down-regulation did not disrupt these complexes, but led DRP1-independent fragmentation...
Tail-anchored proteins form a distinct class of membrane that are found in all intracellular membranes exposed to the cytosol. These have single insertion sequence at their C-terminus and display large N-terminal portion Despite importance for various cellular processes, mechanisms by which these recognized inserted into corresponding target remained largely unclear. Here we address this issue investigate biogenesis tail-anchored residing mitochondrial outer membrane. To goal developed...
Membrane contact sites between endoplasmic reticulum (ER) and mitochondria, mediated by the ER-mitochondria encounter structure (ERMES) complex, are critical for mitochondrial homeostasis cell growth. Defects in ERMES can, however, be bypassed point mutations endosomal protein Vps13 or overexpression of Mcp1. How this bypass operates remains unclear. Here we show that outer membrane Mcp1 functions same pathway as recruiting it to mitochondria promoting its association vacuole-mitochondria...
The mitochondrial outer membrane (MOM) protein Mdm10 is involved in at least three different processes: (i) association of mitochondria with the endoplasmic reticulum and lipid homeostasis, (ii) assembly MOM proteins, (iii) inheritance morphogenesis mitochondria. To decipher precise role function, we screened for high-copy suppressors severe growth defect mdm10Δ mutant. We identified two novel proteins that named complementing (Mcp) 1 Mcp2. Over-expression Mcp1 or Mcp2 restores alterations...
The mitochondrial outer membrane (MOM) harbors several multispan proteins that execute various functions. Despite their importance, the mechanisms by which these are recognized and inserted into remain largely unclear. In this paper, we address issue using yeast mitochondria protein Ugo1. Using a specific insertion assay analysis native gel electrophoresis, show import receptor Tom70, but not its partner Tom20, is involved in initial recognition of Ugo1 precursor. Surprisingly, pore formed...
Most of the mitochondrial outer membrane (MOM) proteins contain helical transmembrane domains. Some single span and all known multiple are inserted into in a pathway which depends on MOM protein Mitochondrial Import 1 (Mim1). So far it has been unknown whether additional required for this process. Here we describe identification characterization Mim2, novel that crucial role biogenesis proteins. Mim2 physically genetically interacts with Mim1 both form MIM complex. Cells lacking exhibit...
Aims: The outer mitochondrial membrane protein Miro1 is a crucial player in dynamics and calcium homeostasis. Recent evidence indicated that mediates calcium-induced shape transition, which prerequisite for the initiation of mitophagy. Moreover, altered levels have emerged as shared feature monogenic sporadic Parkinson's disease (PD), but, so far, no disease-associated variants RHOT1 been identified. Here, we aim to explore genetic functional contribution mutations PD patient-derived...
Most mitochondrial proteins are synthesized in the cytosol prior to their import into organelle. It is commonly accepted that cytosolic factors required for delivering precursor surface and keeping newly an import-competent conformation. However, identity of such defined contribution process mostly unknown. Using a presequence-containing model protein site-directed photo-crosslinking approach yeast cells we identified chaperones Hsp70 (Ssa1) Hsp90 (Hsp82) as well cochaperones, Sti1 Ydj1,...
Mitochondrial distribution and morphology depend on MDM33, a Saccharomyces cerevisiae gene encoding novel protein of the mitochondrial inner membrane. Cells lacking Mdm33 contain ring-shaped, mostly interconnected mitochondria, which are able to form large hollow spheres. On ultrastructural level, these aberrant organelles display extremely elongated stretches outer membranes enclosing very narrow matrix space. Dilated parts Δmdm33 mitochondria well-developed cristae. Overexpression leads...
The MDM31 and MDM32 genes are required for normal distribution morphology of mitochondria in the yeast Saccharomyces cerevisiae. They encode two related proteins located distinct protein complexes mitochondrial inner membrane. Cells lacking Mdm31 Mdm32 harbor giant spherical with highly aberrant internal structure. Mitochondrial DNA (mtDNA) is instable mutants, mtDNA nucleoids disorganized, their association Mmm1-containing outer membrane abolished. Mutant largely immotile, resulting a...
Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are main components mitochondrial membranes. In cell, neutral like triacylglycerides (TAGs) stored in lipid droplets, playing an important role maintaining cellular health. Enzymes lipases mobilize these TAGs according to needs. Neutral have not yet been reported play mitochondria so presence a putative TAG lipase - Tgl2, yeast is surprising. Moreover,...
The TOM complex is the general mitochondrial entry site for newly synthesized proteins. Precursors of β-barrel proteins initially follow this common pathway and are then relayed to SAM/TOB complex, which mediates their integration into outer membrane. Three proteins, Sam50 (Tob55), Sam35 (Tob38/Tom38), Sam37 (Mas37), have been identified as core constituents latter complex. essential growth at elevated temperatures, but function protein currently unresolved. To identify interacting partners...
Assembly and/or insertion of a subset mitochondrial outer membrane (MOM) proteins, including subunits the main MOM translocase, require fungi-specific Mim1/Mim2 complex. So far it was unclear which proteins accomplish this task in other eukaryotes. Here, we show by reciprocal complementation that protein pATOM36 trypanosomes is functional analogue yeast complex, even though these neither sequence nor topological similarity. Expression rescues almost all growth, biogenesis, and morphology...
β-barrel proteins are found in the outer membranes of eukaryotic organelles endosymbiotic origin as well membrane Gram-negative bacteria. Precursors mitochondrial synthesized cytosol and have to be targeted organelle. Currently, signal that assures their specific targeting mitochondria is poorly defined. To characterize structural features needed for test whether a full structure required, we expressed yeast cells domain trimeric autotransporter Yersinia adhesin A (YadA). Trimeric...
The mitochondrial outer membrane (MOM) harbors proteins that traverse the via several helical segments and are called multi-span proteins. To obtain new insights into biogenesis of these proteins, we utilized yeast mitochondria protein Om14. Testing different truncation variants, show while only full-length contains all information assures perfect targeting specificity, shorter variants targeted to with compromised fidelity. Employing a specific insertion assay various deletion strains,...
Mitochondria are unique organelles harboring two distinct membranes, the mitochondrial inner and outer membrane (MIM MOM, respectively). comprise only a subset of metabolic pathways for synthesis lipids; therefore most lipid species their precursors have to be imported from other cellular compartments. One such import process is mediated by ER mitochondria encounter structure (ERMES) complex. Both membranes surround hydrophilic intermembrane space (IMS). Therefore, additional systems...