Pacheu-Grau, David

[["dc.bibliographiccitation.artnumber","64"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Catarino, Claudia B."],["dc.contributor.author","Klopstock, Thomas"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Schittkowski, Michael Peter"],["dc.contributor.author","Wilichowski, Ekkehard"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.issued","2021"],["dc.date.updated","2022-07-29T12:17:42Z"],["dc.description.abstract","Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV. Results We describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control. Conclusions Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Orphanet Journal of Rare Diseases. 2021 Feb 04;16(1):64"],["dc.identifier.doi","10.1186/s13023-021-01690-y"],["dc.identifier.pmid","33541401"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82509"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/219"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.eissn","1750-1172"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Sulthiame"],["dc.subject","Carbonic anhydrase inhibitor"],["dc.subject","Adverse effects"],["dc.subject","Leber hereditary optic neuropathy"],["dc.subject","LHON"],["dc.subject","Oxygen consumption rate"],["dc.title","Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4135"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","4144"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Callegari, Sylvie"],["dc.contributor.author","Emperador, Sonia"],["dc.contributor.author","Thompson, Kyle"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Topol, Sarah E."],["dc.contributor.author","Spencer, Emily G."],["dc.contributor.author","McFarland, Robert"],["dc.contributor.author","Ruiz-Pesini, Eduardo"],["dc.contributor.author","Torkamani, Ali"],["dc.contributor.author","Taylor, Robert W."],["dc.contributor.author","Montoya, Julio"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2019-07-09T11:50:15Z"],["dc.date.available","2019-07-09T11:50:15Z"],["dc.date.issued","2018"],["dc.description.abstract","Protein import into mitochondria is facilitated by translocases within the outer and the inner mitochondrial membranes that are dedicated to a highly specific subset of client proteins. The mitochondrial carrier translocase (TIM22 complex) inserts multispanning proteins, such as mitochondrial metabolite carriers and translocase subunits (TIM23, TIM17A/B and TIM22), into the inner mitochondrial membrane. Both types of substrates are essential for mitochondrial metabolic function and biogenesis. Here, we report on a subject, diagnosed at 1.5 years, with a neuromuscular presentation, comprising hypotonia, gastroesophageal reflux disease and persistently elevated serum and Cerebrospinal fluid lactate (CSF). Patient fibroblasts displayed reduced oxidative capacity and altered mitochondrial morphology. Using trans-mitochondrial cybrid cell lines, we excluded a candidate variant in mitochondrial DNA as causative of these effects. Whole-exome sequencing identified compound heterozygous variants in the TIM22 gene (NM_013337), resulting in premature truncation in one allele (p.Tyr25Ter) and a point mutation in a conserved residue (p.Val33Leu), within the intermembrane space region, of the TIM22 protein in the second allele. Although mRNA transcripts of TIM22 were elevated, biochemical analyses revealed lower levels of TIM22 protein and an even greater deficiency of TIM22 complex formation. In agreement with a defect in carrier translocase function, carrier protein amounts in the inner membrane were found to be reduced. This is the first report of pathogenic variants in the TIM22 pore-forming subunit of the carrier translocase affecting the biogenesis of inner mitochondrial membrane proteins critical for metabolite exchange."],["dc.identifier.doi","10.1093/hmg/ddy305"],["dc.identifier.pmid","30452684"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15894"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59733"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/51"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg"],["dc.relation.issn","1460-2083"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Mutations of the mitochondrial carrier translocase channel subunit TIM22 cause early-onset mitochondrial myopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1747"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Yousefi, Roya"],["dc.contributor.author","Jevdokimenko, Kristina"],["dc.contributor.author","Kluever, Verena"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Fornasiero, Eugenio F."],["dc.date.accessioned","2021-09-01T06:43:07Z"],["dc.date.available","2021-09-01T06:43:07Z"],["dc.date.issued","2021"],["dc.description.abstract","Protein homeostasis is an equilibrium of paramount importance that maintains cellular performance by preserving an efficient proteome. This equilibrium avoids the accumulation of potentially toxic proteins, which could lead to cellular stress and death. While the regulators of proteostasis are the machineries controlling protein production, folding and degradation, several other factors can influence this process. Here, we have considered two factors influencing protein turnover: the subcellular localization of a protein and its functional state. For this purpose, we used an imaging approach based on the pulse-labeling of 17 representative SNAP-tag constructs for measuring protein lifetimes. With this approach, we obtained precise measurements of protein turnover rates in several subcellular compartments. We also tested a selection of mutants modulating the function of three extensively studied proteins, the Ca2+ sensor calmodulin, the small GTPase Rab5a and the brain creatine kinase (CKB). Finally, we followed up on the increased lifetime observed for the constitutively active Rab5a (Q79L), and we found that its stabilization correlates with enlarged endosomes and increased interaction with membranes. Overall, our data reveal that both changes in protein localization and functional state are key modulators of protein turnover, and protein lifetime fluctuations can be considered to infer changes in cellular behavior."],["dc.description.abstract","Protein homeostasis is an equilibrium of paramount importance that maintains cellular performance by preserving an efficient proteome. This equilibrium avoids the accumulation of potentially toxic proteins, which could lead to cellular stress and death. While the regulators of proteostasis are the machineries controlling protein production, folding and degradation, several other factors can influence this process. Here, we have considered two factors influencing protein turnover: the subcellular localization of a protein and its functional state. For this purpose, we used an imaging approach based on the pulse-labeling of 17 representative SNAP-tag constructs for measuring protein lifetimes. With this approach, we obtained precise measurements of protein turnover rates in several subcellular compartments. We also tested a selection of mutants modulating the function of three extensively studied proteins, the Ca2+ sensor calmodulin, the small GTPase Rab5a and the brain creatine kinase (CKB). Finally, we followed up on the increased lifetime observed for the constitutively active Rab5a (Q79L), and we found that its stabilization correlates with enlarged endosomes and increased interaction with membranes. Overall, our data reveal that both changes in protein localization and functional state are key modulators of protein turnover, and protein lifetime fluctuations can be considered to infer changes in cellular behavior."],["dc.description.sponsorship","Schram Stiftung"],["dc.description.sponsorship","DFG"],["dc.identifier.doi","10.3390/cells10071747"],["dc.identifier.pii","cells10071747"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89221"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Influence of Subcellular Localization and Functional State on Protein Turnover"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Yambire, King Faisal"],["dc.contributor.author","Rostosky, Christine"],["dc.contributor.author","Watanabe, Takashi"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Torres-Odio, Sylvia"],["dc.contributor.author","Sanchez-Guerrero, Angela"],["dc.contributor.author","Senderovich, Ola"],["dc.contributor.author","Meyron-Holtz, Esther G"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","West, A Phillip"],["dc.contributor.author","Raimundo, Nuno"],["dc.date.accessioned","2020-12-10T18:48:09Z"],["dc.date.available","2020-12-10T18:48:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.7554/eLife.51031"],["dc.identifier.pmid","31793879"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17114"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79035"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/104"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P02: Charakterisierung der ER-Mitochondrien-Kontakte und ihre Rolle in der Signalweiterleitung"],["dc.relation.workinggroup","RG Milosevic (Synaptic Vesicle Dynamics)"],["dc.relation.workinggroup","RG Raimundo"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","920"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hernández-Reséndiz, Ileana"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Sánchez, Araceli"],["dc.contributor.author","Pardo, Luis A."],["dc.date.accessioned","2021-04-14T08:26:25Z"],["dc.date.available","2021-04-14T08:26:25Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3390/cancers12040920"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81939"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Inhibition of Kv10.1 Channels Sensitizes Mitochondria of Cancer Cells to Antimetabolic Agents"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e32572"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Wang, Cong"],["dc.contributor.author","Chowdhury, Arpita"],["dc.contributor.author","Ronsör, Christin"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Richter-Dennerlein, Ricarda"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2018-05-03T09:03:52Z"],["dc.date.accessioned","2021-10-27T13:21:07Z"],["dc.date.available","2018-05-03T09:03:52Z"],["dc.date.available","2021-10-27T13:21:07Z"],["dc.date.issued","2018"],["dc.description.abstract","Cytochrome c oxidase of the mitochondrial oxidative phosphorylation system reduces molecular oxygen with redox equivalent-derived electrons. The conserved mitochondrial-encoded COX1- and COX2-subunits are the heme- and copper-center containing core subunits that catalyze water formation. COX1 and COX2 initially follow independent biogenesis pathways creating assembly modules with subunit-specific, chaperone-like assembly factors that assist in redox centers formation. Here, we find that COX16, a protein required for cytochrome c oxidase assembly, interacts specifically with newly synthesized COX2 and its copper center-forming metallochaperones SCO1, SCO2, and COA6. The recruitment of SCO1 to the COX2-module is COX16- dependent and patient-mimicking mutations in SCO1 affect interaction with COX16. These findings implicate COX16 in CuA-site formation. Surprisingly, COX16 is also found in COX1-containing assembly intermediates and COX2 recruitment to COX1. We conclude that COX16 participates in merging the COX1 and COX2 assembly lines."],["dc.identifier.doi","10.7554/eLife.32572"],["dc.identifier.gro","3142446"],["dc.identifier.pmid","29381136"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91995"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/200"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation.issn","2050-084X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","COX16 promotes COX2 metallation and assembly during respiratory complex IV biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Peper, Jonas"],["dc.contributor.author","Kownatzki-Danger, Daniel"],["dc.contributor.author","Weninger, Gunnar"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Pronto, Julius Ryan D."],["dc.contributor.author","Sutanto, Henry"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Hindmarsh, Robin"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2021-06-01T09:42:10Z"],["dc.date.available","2021-06-01T09:42:10Z"],["dc.date.issued","2021"],["dc.description.abstract","Rationale: CAV3 (caveolin3) variants associated with arrhythmogenic cardiomyopathy and muscular dystrophy can disrupt post-Golgi surface trafficking. As CAV1 (caveolin1) was recently identified in cardiomyocytes, we hypothesize that conserved isoform-specific protein/protein interactions orchestrate unique cardiomyocyte microdomain functions. To analyze the CAV1 versus CAV3 interactome, we employed unbiased live-cell proximity proteomic, isoform-specific affinity, and complexome profiling mass spectrometry techniques. We demonstrate the physiological relevance and loss-of-function mechanism of a novel CAV3 interactor in gene-edited human induced pluripotent stem cell cardiomyocytes. Objective: To identify differential CAV1 versus CAV3 protein interactions and to define the molecular basis of cardiac CAV3 loss-of-function. Methods and Results: Combining stable isotope labeling with proximity proteomics, we applied mass spectrometry to screen for putative CAV3 interactors in living cardiomyocytes. Isoform-specific affinity proteomic and co-immunoprecipitation experiments confirmed the monocarboxylate transporter McT1 (monocarboxylate transporter type 1) versus aquaporin1, respectively, as CAV3 or CAV1 specific interactors in cardiomyocytes. Superresolution stimulated emission depletion microscopy showed distinct CAV1 versus CAV3 cluster distributions in cardiomyocyte transverse tubules. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9 nuclease)-mediated CAV3 knockout uncovered a stabilizing role for McT1 surface expression, proton-coupled lactate shuttling, increased late Na + currents, and early afterdepolarizations in human induced pluripotent stem cell-derived cardiomyocytes. Complexome profiling confirmed that McT1 and the Na,K-ATPase form labile protein assemblies with the multimeric CAV3 complex. Conclusions: Combining the strengths of proximity and affinity proteomics, we identified isoform-specific CAV1 versus CAV3 binding partners in cardiomyocytes. McT1 represents a novel class of metabolically relevant CAV3-specific interactors close to mitochondria in cardiomyocyte transverse tubules. CAV3 knockout uncovered a previously unknown role for functional stabilization of McT1 in the surface membrane of human cardiomyocytes. Strikingly, CAV3 deficient cardiomyocytes exhibit action potential prolongation and instability, reproducing human reentry arrhythmias in silico. Given that lactate is a major substrate for stress adaption both in the healthy and the diseased human heart, future studies of conserved McT1/CAV3 interactions may provide rationales to target this muscle-specific assembly function therapeutically."],["dc.identifier.doi","10.1161/CIRCRESAHA.119.316547"],["dc.identifier.pmid","33486968"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85167"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/216"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/383"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/135"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1002 | A13: Bedeutung einer gestörten zytosolischen Calciumpufferung bei der atrialen Arrhythmogenese bei Patienten mit Herzinsuffizienz (HF)"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation.eissn","1524-4571"],["dc.relation.issn","0009-7330"],["dc.relation.workinggroup","RG Hasenfuß"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Lenz"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.title","Caveolin3 Stabilizes McT1-Mediated Lactate/Proton Transport in Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","EMBO reports"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Yousefi, Roya"],["dc.contributor.author","Fornasiero, Eugenio F"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Montoya, Julio"],["dc.contributor.author","Jakobs, Stefan"],["dc.contributor.author","Rizzoli, Silvio O"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Pacheu‐Grau, David"],["dc.date.accessioned","2021-04-14T08:28:03Z"],["dc.date.available","2021-04-14T08:28:03Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Mitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system and whose expression is essential for energy production. Information on the regulation and spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we devise an imaging approach to analyze mitochondrial translation within the context of single cells, by following the incorporation of clickable non‐canonical amino acids. We apply this method to multiple cell types, including specialized cells such as cardiomyocytes and neurons, and monitor with spatial resolution mitochondrial translation in axons and dendrites. We also show that translation imaging allows to monitor mitochondrial protein expression in patient fibroblasts. Approaching mitochondrial translation with click chemistry opens new avenues to understand how mitochondrial biogenesis is integrated into the cellular context and can be used to assess mitochondrial gene expression in mitochondrial diseases."],["dc.description.abstract","Synopsis image This study monitors mitochondrial protein synthesis with spatial resolution in single cells of multiple cell types. Labelling of mitochondrial translation products allows to monitor translation with spatial resolution within single cells. Mitochondria show different levels of protein synthesis within a single cell. Protein synthesis occurs in mitochondria of the pre‐ and the postsynapse."],["dc.description.abstract","This study monitors mitochondrial protein synthesis with spatial resolution in single cells of multiple cell types. image"],["dc.description.sponsorship","European Research Council (ERC) http://dx.doi.org/10.13039/501100000781"],["dc.description.sponsorship","Sonderforschungsbereiche (SFB)"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Germany’s Excellence Strategy"],["dc.description.sponsorship","German Federal Ministry of Education and Research (BMBF)/DZHK"],["dc.description.sponsorship","Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587"],["dc.description.sponsorship","Max Planck Institute for Biophysical Chemistry"],["dc.identifier.doi","10.15252/embr.202051635"],["dc.identifier.pmid","33586863"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82485"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/224"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/388"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/107"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A05: Mitochondriale Heterogenität in Synapsen"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation","SFB 1286 | Z03: Unkomplizierte multispektrale, superauflösende Bildgebung durch zehnfache Expansionsmikroskopie"],["dc.relation.eissn","1469-3178"],["dc.relation.issn","1469-221X"],["dc.relation.workinggroup","RG Jakobs (Structure and Dynamics of Mitochondria)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Rizzoli (Quantitative Synaptology in Space and Time)"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.title","Monitoring mitochondrial translation in living cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","244"],["dc.bibliographiccitation.journal","Redox Biology"],["dc.bibliographiccitation.lastpage","254"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Llobet, Laura"],["dc.contributor.author","Bayona-Bafaluy, M. Pilar"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Torres-Pérez, Elena"],["dc.contributor.author","Arbones-Mainar, José M."],["dc.contributor.author","Navarro, M. Ángeles"],["dc.contributor.author","Gómez-Díaz, Covadonga"],["dc.contributor.author","Montoya, Julio"],["dc.contributor.author","López-Gallardo, Ester"],["dc.contributor.author","Ruiz-Pesini, Eduardo"],["dc.date.accessioned","2021-06-01T10:49:54Z"],["dc.date.available","2021-06-01T10:49:54Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1016/j.redox.2017.05.026"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86452"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","2213-2317"],["dc.title","Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Stephan, Till"],["dc.contributor.author","Brüser, Christian"],["dc.contributor.author","Deckers, Markus"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Balzarotti, Francisco"],["dc.contributor.author","Barbot, Mariam"],["dc.contributor.author","Behr, Tiana S."],["dc.contributor.author","Heim, Gudrun"],["dc.contributor.author","Hübner, Wolfgang"],["dc.contributor.author","Ilgen, Peter"],["dc.contributor.author","Lange, Felix"],["dc.contributor.author","Pacheu‐Grau, David"],["dc.contributor.author","Pape, Jasmin K."],["dc.contributor.author","Stoldt, Stefan"],["dc.contributor.author","Huser, Thomas"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Jakobs, Stefan"],["dc.date.accessioned","2021-04-14T08:25:12Z"],["dc.date.available","2021-04-14T08:25:12Z"],["dc.date.issued","2020"],["dc.description.abstract","Mitochondrial function is critically dependent on the folding of the mitochondrial inner membrane into cristae; indeed, numerous human diseases are associated with aberrant crista morphologies. With the MICOS complex, OPA1 and the F1Fo-ATP synthase, key players of cristae biogenesis have been identified, yet their interplay is poorly understood. Harnessing super-resolution light and 3D electron microscopy, we dissect the roles of these proteins in the formation of cristae in human mitochondria. We individually disrupted the genes of all seven MICOS subunits in human cells and re-expressed Mic10 or Mic60 in the respective knockout cell line. We demonstrate that assembly of the MICOS complex triggers remodeling of pre-existing unstructured cristae and de novo formation of crista junctions (CJs) on existing cristae. We show that the Mic60-subcomplex is sufficient for CJ formation, whereas the Mic10-subcomplex controls lamellar cristae biogenesis. OPA1 stabilizes tubular CJs and, along with the F1Fo-ATP synthase, fine-tunes the positioning of the MICOS complex and CJs. We propose a new model of cristae formation, involving the coordinated remodeling of an unstructured crista precursor into multiple lamellar cristae."],["dc.identifier.doi","10.15252/embj.2019104105"],["dc.identifier.pmid","32567732"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81550"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/51"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/115"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/25"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P01: Untersuchung der Unterschiede in der Zusammensetzung, Funktion und Position von individuellen MICOS Komplexen in einzelnen Säugerzellen"],["dc.relation","SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P04: Analyse der räumlichen Organisation der OXPHOS Assemblierung in Säugerzellen"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.relation.workinggroup","RG Hell"],["dc.relation.workinggroup","RG Jakobs (Structure and Dynamics of Mitochondria)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Riedel"],["dc.rights","CC BY 4.0"],["dc.title","MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]