Now showing 1 - 5 of 5
  • 2019Journal Article Research Paper
    [["dc.bibliographiccitation.artnumber","e9561"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Mohanraj, Karthik"],["dc.contributor.author","Wasilewski, Michal"],["dc.contributor.author","Benincá, Cristiane"],["dc.contributor.author","Cysewski, Dominik"],["dc.contributor.author","Poznanski, Jaroslaw"],["dc.contributor.author","Sakowska, Paulina"],["dc.contributor.author","Bugajska, Zaneta"],["dc.contributor.author","Deckers, Markus"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Fernandez‐Vizarra, Erika"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Dadlez, Michal"],["dc.contributor.author","Zeviani, Massimo"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.date.accessioned","2019-07-09T11:51:37Z"],["dc.date.available","2019-07-09T11:51:37Z"],["dc.date.issued","2019"],["dc.description.abstract","Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome c oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency. We found that COA7 requires the mitochondrial IMS import and assembly (MIA) pathway for efficient accumulation in the IMS. We also found that pathogenic mutant versions of COA7 are imported slower than the wild‐type protein, and mislocalized proteins are degraded in the cytosol by the proteasome. Interestingly, proteasome inhibition rescued both the mitochondrial localization of COA7 and complex IV activity in patient‐derived fibroblasts. We propose proteasome inhibition as a novel therapeutic approach for a broad range of mitochondrial pathologies associated with the decreased levels of mitochondrial proteins."],["dc.identifier.doi","10.15252/emmm.201809561"],["dc.identifier.pmid","30885959"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16155"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59974"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/64"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/322424/EU//MITCARE"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/339580/EU//MITRAC"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg"],["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","540"],["dc.title","Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2020-02-13Journal Article Research Paper
    [["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Wasilewski, Michał"],["dc.contributor.author","Oeljeklaus, Silke"],["dc.contributor.author","Gibhardt, Christine Silvia"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Chudenkova, Margarita"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Deckers, Markus"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Warscheid, Bettina"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2020-04-29T13:50:00Z"],["dc.date.available","2020-04-29T13:50:00Z"],["dc.date.issued","2020-02-13"],["dc.description.abstract","The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the CuA site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6, are required for CuA center formation. Loss of function of these chaperones and the concomitant cytochrome c oxidase deficiency cause severe human disorders. Here we analyzed the molecular function of COA6 and the consequences of COA6 deficiency for mitochondria. Our analyses show that loss of COA6 causes combined complex I and complex IV deficiency and impacts membrane potential-driven protein transport across the inner membrane. We demonstrate that COA6 acts as a thiol-reductase to reduce disulfide bridges of critical cysteine residues in SCO1 and SCO2. Cysteines within the CX3CXNH domain of SCO2 mediate its interaction with COA6 but are dispensable for SCO2-SCO1 interaction. Our analyses define COA6 as thiol-reductase, which is essential for CuA biogenesis."],["dc.identifier.doi","10.1016/j.jmb.2020.01.036"],["dc.identifier.pmid","32061935"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/64482"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/339"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/110"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P17: Die Rolle mitochondrialer Kontaktstellen im Rahmen tumorrelevanter Calcium- und Redox-Signalwege"],["dc.relation.eissn","1089-8638"],["dc.relation.issn","0022-2836"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Bogeski"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2011Journal Article Research Paper
    [["dc.bibliographiccitation.firstpage","643"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","656"],["dc.bibliographiccitation.volume","195"],["dc.contributor.author","Schulz, Christian"],["dc.contributor.author","Lytovchenko, Oleksandr"],["dc.contributor.author","Melin, Jonathan"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.contributor.author","Guiard, Bernard"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2017-09-07T11:43:19Z"],["dc.date.available","2017-09-07T11:43:19Z"],["dc.date.issued","2011"],["dc.description.abstract","N-terminal targeting signals (presequences) direct proteins across the TOM complex in the outer mitochondrial membrane and the TIM23 complex in the inner mitochondrial membrane. Presequences provide directionality to the transport process and regulate the transport machineries during translocation. However, surprisingly little is known about how presequence receptors interact with the signals and what role these interactions play during preprotein transport. Here, we identify signal-binding sites of presequence receptors through photo-affinity labeling. Using engineered presequence probes, photo cross-linking sites on mitochondrial proteins were mapped mass spectrometrically, thereby defining a presequence-binding domain of Tim50, a core subunit of the TIM23 complex that is essential for mitochondrial protein import. Our results establish Tim50 as the primary presequence receptor at the inner membrane and show that targeting signals and Tim50 regulate the Tim23 channel in an antagonistic manner."],["dc.identifier.doi","10.1083/jcb.201105098"],["dc.identifier.gro","3142630"],["dc.identifier.isi","000297206400012"],["dc.identifier.pmid","22065641"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8033"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0021-9525"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Tim50's presequence receptor domain is essential for signal driven transport across the TIM23 complex"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC WOS
  • 2018Journal Article
    [["dc.bibliographiccitation.artnumber","4028"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Schendzielorz, Alexander Benjamin"],["dc.contributor.author","Bragoszewski, Piotr"],["dc.contributor.author","Naumenko, Nataliia"],["dc.contributor.author","Gomkale, Ridhima"],["dc.contributor.author","Schulz, Christian"],["dc.contributor.author","Guiard, Bernard"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2020-04-29T13:50:43Z"],["dc.date.available","2020-04-29T13:50:43Z"],["dc.date.issued","2018"],["dc.description.abstract","The presequence translocase of the mitochondrial inner membrane (TIM23 complex) facilitates anterograde precursor transport into the matrix and lateral release of precursors with stop-transfer signal into the membrane (sorting). Sorting requires precursor exit from the translocation channel into the lipid phase through the lateral gate of the TIM23 complex. How the two transport modes are regulated and balanced against each other is unknown. Here we show that the import motor J-protein Pam18, which is essential for matrix import, controls lateral protein release into the lipid bilayer. Constitutively translocase-associated Pam18 obstructs lateral precursor transport. Concomitantly, Mgr2, implicated in precursor quality control, is displaced from the translocase. We conclude that during motor-dependent matrix protein transport, the transmembrane segment of Pam18 closes the lateral gate to promote anterograde polypeptide movement. This finding explains why a motor-free form of the translocase facilitates the lateral movement of precursors with a stop-transfer signal."],["dc.identifier.doi","10.1038/s41467-018-06492-8"],["dc.identifier.pmid","30279421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/64487"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2041-1723"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Motor recruitment to the TIM23 channel's lateral gate restricts polypeptide release into the inner membrane"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2016Journal Article Research Paper
    [["dc.bibliographiccitation.firstpage","4147"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","FEBS Letters"],["dc.bibliographiccitation.lastpage","4158"],["dc.bibliographiccitation.volume","590"],["dc.contributor.author","Callegari, Sylvie"],["dc.contributor.author","Richter, Frank"],["dc.contributor.author","Chojnacka, Katarzyna"],["dc.contributor.author","Jans, Daniel C."],["dc.contributor.author","Lorenzi, Isotta"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Jakobs, Stefan"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2017-09-07T11:53:09Z"],["dc.date.available","2017-09-07T11:53:09Z"],["dc.date.issued","2016"],["dc.description.abstract","Hydrophobic inner mitochondrial membrane proteins with internal targeting signals, such as the metabolite carriers, use the carrier translocase (TIM22 complex) for transport into the inner membrane. Defects in this transport pathway have been associated with neurodegenerative disorders. While the TIM22 complex is well studied in baker's yeast, very little is known about the mammalian TIM22 complex. Using immunoprecipitation, we purified the human carrier translocase and identified a mitochondrial inner membrane protein TIM29 as a novel component, specific to metazoa. We show that TIM29 is a constituent of the 440 kDa TIM22 complex and interacts with oxidized TIM22. Our analyses demonstrate that TIM29 is required for the structural integrity of the TIM22 complex and for import of substrate proteins by the carrier translocase."],["dc.identifier.doi","10.1002/1873-3468.12450"],["dc.identifier.fs","625768"],["dc.identifier.gro","3145043"],["dc.identifier.pmid","27718247"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14166"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2736"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/59"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["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","SFB 1190 | Z02: Massenspektrometrie-basierte Proteomanalyse"],["dc.relation.issn","0014-5793"],["dc.relation.workinggroup","RG Jakobs (Structure and Dynamics of Mitochondria)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","TIM29 is a subunit of the human carrier translocase required for protein transport"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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