Aich, Abhishek

[["dc.bibliographiccitation.firstpage","323"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta"],["dc.bibliographiccitation.lastpage","333"],["dc.bibliographiccitation.volume","1865"],["dc.contributor.author","Lorenzi, Isotta"],["dc.contributor.author","Oeljeklaus, Silke"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Ronsör, Christin"],["dc.contributor.author","Callegari, Sylvie"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Warscheid, Bettina"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2018-01-09T14:12:01Z"],["dc.date.available","2018-01-09T14:12:01Z"],["dc.date.issued","2018"],["dc.description.abstract","The three mitochondrial-encoded proteins, COX1, COX2, and COX3, form the core of the cytochrome c oxidase. Upon synthesis, COX2 engages with COX20 in the inner mitochondrial membrane, a scaffold protein that recruits metallochaperones for copper delivery to the CuA-Site of COX2. Here we identified the human protein, TMEM177 as a constituent of the COX20 interaction network. Loss or increase in the amount of TMEM177 affects COX20 abundance leading to reduced or increased COX20 levels respectively. TMEM177 associates with newly synthesized COX2 and SCO2 in a COX20-dependent manner. Our data shows that by unbalancing the amount of TMEM177, newly synthesized COX2 accumulates in a COX20-associated state. We conclude that TMEM177 promotes assembly of COX2 at the level of CuA-site formation."],["dc.identifier.doi","10.1016/j.bbamcr.2017.11.010"],["dc.identifier.pmid","29154948"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15209"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11600"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/16"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["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-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nd/4.0"],["dc.title","The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","4284"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Walter, Corvin"],["dc.contributor.author","Marada, Adinarayana"],["dc.contributor.author","Suhm, Tamara"],["dc.contributor.author","Ernsberger, Ralf"],["dc.contributor.author","Muders, Vera"],["dc.contributor.author","Kücükköse, Cansu"],["dc.contributor.author","Sánchez-Martín, Pablo"],["dc.contributor.author","Hu, Zehan"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Loroch, Stefan"],["dc.contributor.author","Meisinger, Chris"],["dc.date.accessioned","2021-09-01T06:42:23Z"],["dc.date.available","2021-09-01T06:42:23Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70 Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70 Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A , including autism spectrum disorder, microcephaly and Down syndrome."],["dc.identifier.doi","10.1038/s41467-021-24426-9"],["dc.identifier.pii","24426"],["dc.identifier.pmid","34257281"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89043"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/398"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.title","Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6530"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Ternka, Katharina"],["dc.contributor.author","Wendland, Kristin"],["dc.contributor.author","Krüger, Dennis Manfred"],["dc.contributor.author","Zampar, Silvia"],["dc.contributor.author","Schob, Charlotte"],["dc.contributor.author","Franz, Jonas"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Sakib, M. Sadman"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-12-01T09:23:01Z"],["dc.date.available","2021-12-01T09:23:01Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2 −/− mice using CRISPR/Cas9-mediated genome editing. Rnaset2 −/− mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8 + effector memory T cells and inflammatory monocytes into the grey and white matter. Single nuclei RNA sequencing reveals homeostatic dysfunctions in glial cells and neurons and provide important insights into the mechanisms of hippocampal-accentuated brain atrophy and cognitive impairment. The Rnaset2 −/− mice may allow the study of CNS damage associated with RNaseT2 deficiency and may be used for the investigation of potential therapies."],["dc.identifier.doi","10.1038/s41467-021-26880-x"],["dc.identifier.pii","26880"],["dc.identifier.pmid","34764281"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94539"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/361"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/48"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/141"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Gärtner"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.rights","CC BY 4.0"],["dc.title","Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy"],["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","598"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","614"],["dc.bibliographiccitation.volume","218"],["dc.contributor.author","Richter, Frank"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Nikolov, Miroslav"],["dc.contributor.author","Jans, Daniel C."],["dc.contributor.author","Naumenko, Nataliia"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","MacVicar, Thomas"],["dc.contributor.author","Linden, Andreas"],["dc.contributor.author","Jakobs, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Langer, Thomas"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2019-07-09T11:50:27Z"],["dc.date.available","2019-07-09T11:50:27Z"],["dc.date.issued","2019"],["dc.description.abstract","The mitochondrial presequence translocation machinery (TIM23 complex) is conserved between the yeast Saccharomyces cerevisiae and humans; however, functional characterization has been mainly performed in yeast. Here, we define the constituents of the human TIM23 complex using mass spectrometry and identified ROMO1 as a new translocase constituent with an exceptionally short half-life. Analyses of a ROMO1 knockout cell line revealed aberrant inner membrane structure and altered processing of the GTPase OPA1. We show that in the absence of ROMO1, mitochondria lose the inner membrane YME1L protease, which participates in OPA1 processing and ROMO1 turnover. While ROMO1 is dispensable for general protein import along the presequence pathway, we show that it participates in the dynamics of TIM21 during respiratory chain biogenesis and is specifically required for import of YME1L. This selective import defect can be linked to charge distribution in the unusually long targeting sequence of YME1L. Our analyses establish an unexpected link between mitochondrial protein import and inner membrane protein quality control."],["dc.identifier.doi","10.1083/jcb.201806093"],["dc.identifier.pmid","30598479"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59776"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/339580/EU//MITRAC"],["dc.relation.issn","1540-8140"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","ROMO1 is a constituent of the human presequence translocase required for YME1L protease import"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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.firstpage","5824"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","5837.e15"],["dc.bibliographiccitation.volume","184"],["dc.contributor.author","Cruz-Zaragoza, Luis Daniel"],["dc.contributor.author","Dennerlein, Sven"],["dc.contributor.author","Linden, Andreas"],["dc.contributor.author","Yousefi, Roya"],["dc.contributor.author","Lavdovskaia, Elena"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Falk, Rebecca R."],["dc.contributor.author","Gomkale, Ridhima"],["dc.contributor.author","Schöndorf, Thomas"],["dc.contributor.author","Bohnsack, Markus T."],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2021-12-01T09:23:52Z"],["dc.date.available","2021-12-01T09:23:52Z"],["dc.date.issued","2021"],["dc.description.abstract","The human mitochondrial genome encodes thirteen core subunits of the oxidative phosphorylation system, and defects in mitochondrial gene expression lead to severe neuromuscular disorders. However, the mechanisms of mitochondrial gene expression remain poorly understood due to a lack of experimental approaches to analyze these processes. Here, we present an in vitro system to silence translation in purified mitochondria. In vitro import of chemically synthesized precursor-morpholino hybrids allows us to target translation of individual mitochondrial mRNAs. By applying this approach, we conclude that the bicistronic, overlapping ATP8/ATP6 transcript is translated through a single ribosome/mRNA engagement. We show that recruitment of COX1 assembly factors to translating ribosomes depends on nascent chain formation. By defining mRNA-specific interactomes for COX1 and COX2, we reveal an unexpected function of the cytosolic oncofetal IGF2BP1, an RNA-binding protein, in mitochondrial translation. Our data provide insight into mitochondrial translation and innovative strategies to investigate mitochondrial gene expression."],["dc.identifier.doi","10.1016/j.cell.2021.09.033"],["dc.identifier.pii","S0092867421011168"],["dc.identifier.pmid","34672953"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94777"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/355"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/161"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation.issn","0092-8674"],["dc.relation.workinggroup","RG M. Bohnsack (Molecular Biology)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Richter-Dennerlein (Mitoribosome Assembly)"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.rights","CC BY 4.0"],["dc.title","An in vitro system to silence mitochondrial gene expression"],["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","561"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","570.e6"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Chowdhury, Arpita"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Wozny, Katharina"],["dc.contributor.author","Lüchtenborg, Christian"],["dc.contributor.author","Hartmann, Magnus"],["dc.contributor.author","Bernhard, Olaf"],["dc.contributor.author","Balleiniger, Martina"],["dc.contributor.author","Alfar, Ezzaldin Ahmed"],["dc.contributor.author","Zieseniß, Anke"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Rizzoli, Silvio O."],["dc.contributor.author","Brügger, Britta"],["dc.contributor.author","Fischer, Andrè"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Dudek, Jan"],["dc.date.accessioned","2019-01-17T15:41:24Z"],["dc.date.available","2019-01-17T15:41:24Z"],["dc.date.issued","2018"],["dc.description.abstract","Summary: Mitochondria fulfill vital metabolic functions and act as crucial cellular signaling hubs, integrating their metabolic status into the cellular context. Here, we show that defective cardiolipin remodeling, upon loss of the cardiolipin acyl transferase tafazzin, decreases HIF-1α signaling in hypoxia. Tafazzin deficiency does not affect posttranslational HIF-1α regulation but rather HIF-1α gene expression, a dysfunction recapitulated in iPSC-derived cardiomyocytes from Barth syndrome patients with tafazzin deficiency. RNA-seq analyses confirmed drastically altered signaling in tafazzin mutant cells. In hypoxia, tafazzin-deficient cells display reduced production of reactive oxygen species (ROS) perturbing NF-κB activation and concomitantly HIF-1α gene expression. Tafazzin-deficient mice hearts display reduced HIF-1α levels and undergo maladaptive hypertrophy with heart failure in response to pressure overload challenge. We conclude that defective mitochondrial cardiolipin remodeling dampens HIF-1α signaling due to a lack of NF-κB activation through reduced mitochondrial ROS production, decreasing HIF-1α transcription."],["dc.identifier.doi","10.1016/j.celrep.2018.09.057"],["dc.identifier.pmid","30332638"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15391"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57349"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/237"],["dc.language.iso","en"],["dc.notes.intern","Merged 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","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.issn","2211-1247"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Defective Mitochondrial Cardiolipin Remodeling Dampens HIF-1α Expression in Hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","269"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of molecular medicine (Berlin, Germany)"],["dc.bibliographiccitation.lastpage","279"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Antunes, Diana"],["dc.contributor.author","Chowdhury, Arpita"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Saladi, Sreedivya"],["dc.contributor.author","Harpaz, Nofar"],["dc.contributor.author","Stahl, Mark"],["dc.contributor.author","Schuldiner, Maya"],["dc.contributor.author","Herrmann, Johannes M."],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Rapaport, Doron"],["dc.date.accessioned","2019-08-07T11:33:10Z"],["dc.date.available","2019-08-07T11:33:10Z"],["dc.date.issued","2019"],["dc.description.abstract","The yeast protein Taz1 is the orthologue of human Tafazzin, a phospholipid acyltransferase involved in cardiolipin (CL) remodeling via a monolyso CL (MLCL) intermediate. Mutations in Tafazzin lead to Barth syndrome (BTHS), a metabolic and neuromuscular disorder that primarily affects the heart, muscles, and immune system. Similar to observations in fibroblasts and platelets from patients with BTHS or from animal models, abolishing yeast Taz1 results in decreased total CL amounts, increased levels of MLCL, and mitochondrial dysfunction. However, the biochemical mechanisms underlying the mitochondrial dysfunction in BTHS remain unclear. To better understand the pathomechanism of BTHS, we searched for multi-copy suppressors of the taz1Δ growth defect in yeast cells. We identified the branched-chain amino acid transaminases (BCATs) Bat1 and Bat2 as such suppressors. Similarly, overexpression of the mitochondrial isoform BCAT2 in mammalian cells lacking TAZ improves their growth. Elevated levels of Bat1 or Bat2 did not restore the reduced membrane potential, altered stability of respiratory complexes, or the defective accumulation of MLCL species in yeast taz1Δ cells. Importantly, supplying yeast or mammalian cells lacking TAZ1 with certain amino acids restored their growth behavior. Hence, our findings suggest that the metabolism of amino acids has an important and disease-relevant role in cells lacking Taz1 function. KEY MESSAGES: Bat1 and Bat2 are multi-copy suppressors of retarded growth of taz1Δ yeast cells. Overexpression of Bat1/2 in taz1Δ cells does not rescue known mitochondrial defects. Supplementation of amino acids enhances growth of cells lacking Taz1 or Tafazzin. Altered metabolism of amino acids might be involved in the pathomechanism of BTSH."],["dc.identifier.doi","10.1007/s00109-018-1728-4"],["dc.identifier.pmid","30604168"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62341"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/250"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation.eissn","1432-1440"],["dc.relation.issn","0946-2716"],["dc.relation.issn","1432-1440"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.title","Overexpression of branched-chain amino acid aminotransferases rescues the growth defects of cells lacking the Barth syndrome-related gene TAZ1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]