PXD028516

PXD028516 is an original dataset announced via ProteomeXchange.

Title	importance of MTFP1 for mitochondrial function in the heart
Description	Mitochondria 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
HostingRepository	PRIDE
AnnounceDate	2022-10-06
AnnouncementXML	Submission_2022-10-06_10:21:31.443.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	thibault chaze
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 02:56:10	ID requested
⏵ 1	2022-10-06 10:21:31	announced

Dataset with its publication pending

submitter keyword: mouse, heart, mitochondria

Mariette matondo
contact affiliation	Institut Pasteur 25 Rue du Docteur Roux Paris 75015
contact email	mariette.matondo@pasteur.fr
lab head
thibault chaze
contact affiliation	Institut Pasteur
contact email	thibault.chaze@pasteur.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028516
     1. Label: PRIDE project
     2. Name: importance of MTFP1 for mitochondrial function in the heart