PXD022689-1

PXD022689 is an original dataset announced via ProteomeXchange.

Title	Calpain-mediated Protein Targets in Cardiac Mitochondria following Ischemia-Reperfusion
Description	Calpain 1 and 2 (CPN1/2) are calcium-dependent cysteine proteases that exist in cytosol and mitochondria. Pharmacologic inhibition of CPN1/2 decreases cardiac injury during ischemia (ISC) – reperfusion (REP) by improving mitochondrial function. However, the protein targets of CPN1/2 activation during ISC-REP are unclear. CPN1/2 include a large subunit and a small regulatory subunit 1 (CPNS1). Genetic deletion of the CPNS1 eliminates the activities of both CPN1 and CPN2. Conditional, cardiomyocyte specific CPNS1 knockout (KO) mice were used in the present study to clarify the role of CPN1/2 activation in mitochondrial damage during ISC-REP with an emphasis on identifying the potential protein targets of CPN1/2. Isolated hearts from wild type (WT) or CPNS1 KO mice underwent 25 min in vitro global ISC and 30 min REP. LDH activity in coronary effluent was measured to reflect cardiac injury. Mitochondria were isolated from the hearts. Cardiac injury was decreased in CPNS1 KO mice following ISC-REP compared to WT. ISC-REP decreased the rate of oxidative phosphorylation in WT but not in CPNS1 KO mice when glutamate + malate was used as complex I substrate. KO of CPNS1 led to a smaller decrease in CRC (calcium retention capacity) following REP compared to WT. The H2O2 generation was decreased in KO mitochondria following ISC-REP compared to WT. KO of CPNS1 also resulted in less cytochrome c release from mitochondria. Proteomic analysis of the isolated mitochondria showed that KO of CPNS1 increased the abundance of ribosomal proteins and mitochondrial biogenesis proteins. These results show that activation of CPN1/2 increases cardiac injury during ischemia-reperfusion by damaging mitochondria.
HostingRepository	PRIDE
AnnounceDate	2021-12-21
AnnouncementXML	Submission_2021-12-21_07:42:45.146.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022689
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-24 07:50:05	ID requested
⏵ 1	2021-12-21 07:42:45	announced

Dataset with its publication pending

submitter keyword: calpain

mitochondrial respiratory chain

reactive oxygen species, reverse electron flow

Qun Chen
contact affiliation	Departments of Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA, 23298
contact email	qun.chen@vcuhealth.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022689
     1. Label: PRIDE project
     2. Name: Calpain-mediated Protein Targets in Cardiac Mitochondria following Ischemia-Reperfusion