<?xml version="1.0" encoding="UTF-8" standalone="yes"?> <ProteomeXchangeDataset id="PXD037987" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <CvList> <Cv fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-CV/master/psi-ms.obo" id="MS"/> <Cv fullName="PSI-MOD" uri="https://raw.githubusercontent.com/MICommunity/psidev/master/psi/mod/data/PSI-MOD.obo" id="MOD"/> <Cv fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo" id="UNIMOD"/> </CvList> <DatasetSummary announceDate="2023-04-21" hostingRepository="PRIDE" title="IDH3 serves as a redox switch that regulates mitochondrial energy metabolism and contractility in the heart under oxidative stress"> <Description>Redox signaling and cardiac function are tightly linked. Still, it is largely unknown which specific protein targets are affected by reactive oxygen species (ROS) that underly the impaired inotropic effect in oxidative stress. Here, we combined a new chemogenetic mouse model (HMC HyPer-DAO transgenic mice) and a redox proteomics approach to identify cellular redox switches and their functional role. Using the HyPer-DAO mice, we prove that increased endogenous production of H2O2 in cardiomyocytes is leading to a reversible cardiac contractility in vivo. We identified the -subunit of the TCA cycle enzyme isocitrate dehydrogenase (IDH)3 as a redox switch and linked this modification to mitochondrial metabolism and glutathione synthesis. Molecular dynamics simulations combined with experimental evidence from cysteine-gene-edited point mutations revealed that IDH3 Cys148 and 284 are critically involved in oxidant-dependent alterations of IDH3 function. Together, our results demonstrate a specific link between ROS, IDH3 and mitochondrial metabolism. Cardiac phenotyping of the chemogenetic mice reveal the biological significance of these ROS-induced modifications.</Description> <ReviewLevel> <cvParam cvRef="MS" accession="MS:1002854" name="Peer-reviewed dataset"/> </ReviewLevel> <RepositorySupport> <cvParam cvRef="MS" accession="MS:1002856" name="Supported dataset by repository"/> </RepositorySupport> </DatasetSummary> <DatasetIdentifierList> <DatasetIdentifier> <cvParam cvRef="MS" accession="MS:1001919" name="ProteomeXchange accession number" value="PXD037987"/> </DatasetIdentifier> <DatasetIdentifier> <cvParam cvRef="MS" accession="MS:1001922" name="Digital Object Identifier (DOI)" value="10.6019/PXD037987"/> </DatasetIdentifier> </DatasetIdentifierList> <DatasetOriginList> <DatasetOrigin> <cvParam cvRef="MS" accession="MS:1002868" name="Original data"/> </DatasetOrigin> </DatasetOriginList> <SpeciesList> <Species> <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Mus musculus (Mouse)"/> <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="10090"/> </Species> </SpeciesList> <InstrumentList> <Instrument id="Instrument_1"> <cvParam cvRef="MS" accession="MS:1003029" name="Orbitrap Eclipse"/> </Instrument> </InstrumentList> <ModificationList> <cvParam cvRef="MOD" accession="MOD:00425" name="monohydroxylated residue"/> </ModificationList> <ContactList> <Contact id="project_submitter"> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="JingyunLee"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="jilee@wakehealth.edu"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="Wake Forest Baptist Health"/> <cvParam cvRef="MS" accession="MS:1002037" name="dataset submitter"/> </Contact> <Contact id="project_lab_head"> <cvParam cvRef="MS" accession="MS:1002332" name="lab head"/> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Cristina M.Furdui"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="cfurdui@wakehealth.edu"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States"/> </Contact> </ContactList> <PublicationList> <Publication id="PMID37055412"> <cvParam cvRef="MS" accession="MS:1000879" name="PubMed identifier" value="37055412"/> <cvParam cvRef="MS" accession="MS:1002866" name="Reference" value="Nanadikar MS, Vergel Leon AM, Guo J, van Belle GJ, Jatho A, Philip ES, Brandner AF, Böckmann RA, Shi R, Zieseniss A, Siemssen CM, Dettmer K, Brodesser S, Schmidtendorf M, Lee J, Wu H, Furdui CM, Brandenburg S, Burgoyne JR, Bogeski I, Riemer J, Chowdhury A, Rehling P, Bruegmann T, Belousov VV, Katschinski DM. IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart. Nat Commun. 2023 14(1):2123"/> </Publication> <Publication id="DOI-10_6019_PXD037987"> <cvParam cvRef="MS" accession="MS:1001922" name="Digital Object Identifier (DOI)" value="10.6019/PXD037987"/> </Publication> </PublicationList> <KeywordList> <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="heart,Mouse, HyPerDAO, redox proteomics"/> </KeywordList> <FullDatasetLinkList> <FullDatasetLink> <cvParam cvRef="MS" accession="MS:1002852" name="Dataset FTP location" value="ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD037987"/> </FullDatasetLink> <FullDatasetLink> <cvParam cvRef="MS" accession="MS:1001930" name="PRIDE project URI" value="http://www.ebi.ac.uk/pride/archive/projects/PXD037987"/> </FullDatasetLink> </FullDatasetLinkList> <DatasetFileList> <DatasetFile id="FILE_1" name="20220803__HyperDAO_TRO_03.raw"> <cvParam cvRef="MS" accession="MS:1002846" name="Associated raw file URI" 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