PXD037987-2

PXD037987 is an original dataset announced via ProteomeXchange.

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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:57.947.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037987
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jingyun Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-07 08:49:45	ID requested
1	2023-04-21 07:35:58	announced
⏵ 2	2023-11-14 08:45:07	announced	2023-11-14: Updated project metadata.

10.6019/PXD037987;

Nanadikar MS, Vergel Leon AM, Guo J, van Belle GJ, Jatho A, Philip ES, Brandner AF, B, ö, ckmann 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, functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart. Nat Commun, 14(1):2123(2023) [pubmed]

submitter keyword: heart,Mouse, HyPerDAO, redox proteomics

Cristina M. Furdui
contact affiliation	Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
contact email	cfurdui@wakehealth.edu
lab head
Jingyun Lee
contact affiliation	Wake Forest Baptist Health
contact email	jilee@wakehealth.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037987
     1. Label: PRIDE project
     2. Name: IDH3 serves as a redox switch that regulates mitochondrial energy metabolism and contractility in the heart under oxidative stress