PXD034771-1

PXD034771 is an original dataset announced via ProteomeXchange.

Title	Inhibition of mammalian mtDNA transcription in liver reprograms metabolism to reverse diet-induced obesity and hepatosteatosis
Description	The oxidative phosphorylation (OXPHOS) system in mammalian mitochondria plays a key role in harvesting energy from different types of ingested nutrients1,2. Mitochondrial metabolism is very dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states3. Rewiring of mitochondrial metabolism is intricately linked to common metabolic diseases4–6 and is also necessary to promote tumor growth7–11. Here, we demonstrate that per oral treatment of mice with an inhibitor of mitochondrial transcription (IMT)11 leads to a profound inhibition of mtDNA expression in the liver, which markedly reduces complex I levels of the OXPHOS system, whereas the levels of electron transfer flavoprotein dehydrogenase (ETF-DH) and other dehydrogenases that feeds electrons into the ubiquinone (Q) pool remain unaltered or are increased. Deep pProteomics and non-targeted metabolomics analyses of liver reveal that IMT-treatment rewires the OXPHOS system to activates fatty acid oxidation in mice regardless of the diet. Remarkably, treatment of high fat diet (HFD)-fed mice with IMTs rapidly normalizes body weight, reverses hepatosteatosis and restores glucose tolerance. We thus propose a novel treatment principle of obesity and diabetes based on inhibition of mtDNA transcription to accomplish a rewiring of mitochondrial metabolism to favor fatty acid degradation.
HostingRepository	PRIDE
AnnounceDate	2024-03-28
AnnouncementXML	Submission_2024-03-28_02:42:14.050.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-21 01:20:11	ID requested
⏵ 1	2024-03-28 02:42:14	announced
2	2024-10-22 06:34:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Mitochondria, POLRMT,Liver, IMT, hepatosteatosis, diabetes

Nils-Göran Larsson
contact affiliation	Karolinska Institute Division of Molecular Metabolism Department of Medical Biochemistry and Biophysics
contact email	nils-goran.larsson@ki.se
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.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/2024/03/PXD034771

PRIDE project URI

• PRIDE
  1. PXD034771
     1. Label: PRIDE project
     2. Name: Inhibition of mammalian mtDNA transcription in liver reprograms metabolism to reverse diet-induced obesity and hepatosteatosis