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PXD034477 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHepatic deletion of Mtfp1 enhances oxidative phosphorylation and cell death resistance to confer protection against liver disease _ REVISION
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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-10 08:24:37ID requested
12022-10-05 06:39:04announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Mouse, LFQ, liver disease
Contact List
Timoty Wai
contact affiliationMitochondrial biology group, Institut Pasteur, Paris
contact emailtimoty.wai@pasteur.fr
lab head
contact affiliationPasteur
contact emailmariette.matondo@pasteur.fr
dataset submitter
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Dataset FTP location
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