PXD053562

PXD053562 is an original dataset announced via ProteomeXchange.

Title	Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure
Description	The presence of redox-active molecules containing catenated sulfur atoms (supersulfide) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body’s primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in mice by electrophilic modification of dynamin-related protein (Drp1). In healthy exercised hearts, the redox-sensitive Cys644 of Drp1 is highly S-glutathionylated. Nearly 40 % of Cys644 is normally polysulfidated, and Cys644 S-glutathionylation is resistant to Drp1 depolysulfidation-dependent mitochondrial hyperfission and myocardial dysfunction caused by hypoxic or environmental chemical stress. MD simulation of Drp1 structure and site-directed mutagenetic analysis reveals a functional interaction between Cys644 and a critical phosphorylation site Ser637, through Glu640. Bulky modification at Cys644 via polysulfidation or S-glutathionylation reduces Drp1 activity by disrupting Ser637-Glu640-Cys644 interaction. Disruption of Cys644 S-glutathionylation nullifies the cardioprotective effect of GSSG against heart failure after myocardial infarction. Our findings suggest a novel therapeutic potential of polysulfur-based Cys bulking on Drp1 for ischemic heart disease.
HostingRepository	PRIDE
AnnounceDate	2024-11-16
AnnouncementXML	Submission_2024-11-15_19:39:15.365.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Seiryo Ogata
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	6520A Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-02 04:14:58	ID requested
⏵ 1	2024-11-15 19:39:15	announced

Dataset with its publication pending

submitter keyword: Mitochondria,Glutathionylation, heart failure, Drp1, Supersulfide catabolism

Takaaki Akaike
contact affiliation	Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
contact email	takaike@med.tohoku.ac.jp
lab head
Seiryo Ogata
contact affiliation	Tohoku University
contact email	sogata@med.tohoku.ac.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053562
     1. Label: PRIDE project
     2. Name: Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure