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PXD028516

PXD028516 is an original dataset announced via ProteomeXchange.

Dataset Summary
Titleimportance of MTFP1 for mitochondrial function in the heart
DescriptionMitochondria are paramount to the metabolism and survival of cardiomyocytes. Here we show that Mitochondrial Fission Process 1 (MTFP1) is essential for cardiac structure and function. Constitutive knockout of cardiomyocyte MTFP1 in mice resulted in adult-onset dilated cardiomyopathy (DCM) characterized by sterile inflammation and cardiac fibrosis that progressed to heart failure and middle-aged death. Failing hearts from cardiomyocyte-restricted knockout mice displayed a general decline in mitochondrial gene expression and oxidative phosphorylation (OXPHOS) activity. Pre-DCM, we observed no defects in mitochondrial morphology, content, gene expression, OXPHOS assembly nor phosphorylation dependent respiration. However, knockout cardiac mitochondria displayed reduced membrane potential and increased non-phosphorylation dependent respiration, which could be rescued by pharmacological inhibition of the adenine nucleotide translocase ANT. Primary cardiomyocytes from pre-symptomatic knockout mice exhibited normal excitation-contraction coupling but increased sensitivity to programmed cell death (PCD), which was accompanied by an opening of the mitochondrial permeability transition pore (mPTP). Intriguingly, mouse embryonic fibroblasts deleted for Mtfp1 recapitulated PCD sensitivity and mPTP opening, both of which could be rescued by pharmacological or genetic inhibition of the mPTP regulator Cyclophilin D. Collectively, our data demonstrate that contrary to previous in vitro studies, the loss of the MTFP1 promotes mitochondrial uncoupling and increases cell death sensitivity, causally mediating pathogenic cardiac remodeling
HostingRepositoryPRIDE
AnnounceDate2022-10-06
AnnouncementXMLSubmission_2022-10-06_10:21:31.443.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterthibault chaze
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-16 02:56:10ID requested
12022-10-06 10:21:31announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: mouse, heart, mitochondria
Contact List
Mariette matondo
contact affiliationInstitut Pasteur 25 Rue du Docteur Roux Paris 75015
contact emailmariette.matondo@pasteur.fr
lab head
thibault chaze
contact affiliationInstitut Pasteur
contact emailthibault.chaze@pasteur.fr
dataset submitter
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Dataset FTP location
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