PXD031324-1

PXD031324 is an original dataset announced via ProteomeXchange.

Title	FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction
Description	Mitochondrial integrated stress response emerged as a major adaptive pathway to respiratory chain deficiency, but tissue-specifics of its regulation or how it adapts to different levels of mitochondrial dysfunction are largely unknown. Here we report that diverse levels of mitochondrial cardiomyopathy activate mitoISR, including high production of FGF21, a cytokine with both paracrine and endocrine function, shown to be induced by respiratory chain dysfunction. Remarkably, although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of the mitoISR. In the absence of FGF21, a large part of the metabolic adaptation to mitochondrial dysfunction (one-carbon metabolism, transsulfuration and serine and proline biosynthesis) is strongly blunted, independent of the primary mitoISR activator ATF4. Collectively, our work highlights the complexity of mitochondrial stress responses by revealing the importance of the tissue-specificity and dose-dependency of the mitoISR.
HostingRepository	PRIDE
AnnounceDate	2022-04-27
AnnouncementXML	Submission_2022-04-27_02:35:08.437.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Theresa Bock
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	2022-01-30 10:52:47	ID requested
⏵ 1	2022-04-27 02:35:09	announced

Croon M, Szczepanowska K, Popovic M, Lienkamp C, Senft K, Brandscheid CP, Bock T, Gnatzy-Feik L, Ashurov A, Acton RJ, Kaul H, Pujol C, Rosenkranz S, Kr, ü, ger M, Trifunovic A, FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction. Sci Adv, 8(14):eabn7105(2022) [pubmed]

submitter keyword: Mitochondria, Cardiomyopathy, FGF21, CLPP, OXPHOS

Aleksandra Trifunovic
contact affiliation	Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, D-50931 Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, 50931 Cologne, Germany
contact email	aleksandra.trifunovic@uk-koeln.de
lab head
Theresa Bock
contact affiliation	CECAD Research Center, University of Cologne
contact email	tbock2@uni-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/04/PXD031324

PRIDE project URI

• PRIDE
  1. PXD031324
     1. Label: PRIDE project
     2. Name: FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction