PXD034477

PXD034477 is an original dataset announced via ProteomeXchange.

Title	Hepatic deletion of Mtfp1 enhances oxidative phosphorylation and cell death resistance to confer protection against liver disease _ REVISION
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	2022-10-05
AnnouncementXML	Submission_2022-10-05_06:39:04.098.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MARIETTE MATONDO
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	2022-06-10 08:24:37	ID requested
⏵ 1	2022-10-05 06:39:04	announced

Dataset with its publication pending

submitter keyword: Mouse, LFQ, liver disease

Timoty Wai
contact affiliation	Mitochondrial biology group, Institut Pasteur, Paris
contact email	timoty.wai@pasteur.fr
lab head
MARIETTE MATONDO
contact affiliation	Pasteur
contact email	mariette.matondo@pasteur.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034477
     1. Label: PRIDE project
     2. Name: Hepatic deletion of Mtfp1 enhances oxidative phosphorylation and cell death resistance to confer protection against liver disease _ REVISION