PXD032214

PXD032214 is an original dataset announced via ProteomeXchange.

Title	Adaption of oxidative phosphorylation machinery compensates hepatic lipotoxicity in early stages of MAFLD
Description	Mitochondrial function is an important control variable in the progression of metabolic dysfunction associated fatty liver disease (MAFLD). We hypothesize that organization and function of mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. Paradoxically, in MAFLD increased de novo lipogenesis (DNL) occurs despite hepatic insulin resistance. Therefore, we addressed this question using our animal model alb-SREBP-1c, which exhibits increased DNL by constitutively active SREBP-1c. Using an omics approach, we show that the abundance of ETC complex subunits and metabolic pathways are altered in liver of these animals. Analyses of cellular metabolic status by functional assays revealed that SREBP-1c-forced DNL induces a limitation of substrates for oxidative phosphorylation that is rescued by enhanced complex II activity. Furthermore, energy metabolism associated gene regulation indicates the counteracting to increase expression of mitochondrial genes and features cell communication by miRNA and exosomal RNA transfer. In conclusion, substrate availability fuels mainly complex II electron flows as a consequence of activated DNL with impact on whole body by liver-specific exosomal RNAs in early stages of MAFLD.
HostingRepository	PRIDE
AnnounceDate	2022-08-02
AnnouncementXML	Submission_2022-08-02_03:59:12.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Birgit Knebel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-11 09:52:39	ID requested
⏵ 1	2022-08-02 03:59:13	announced

Fahlbusch P, Nikolic A, Hartwig S, Jacob S, Kettel U, K, ö, llmer C, Al-Hasani H, Lehr S, M, ü, ller-Wieland D, Knebel B, Kotzka J, Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD. Int J Mol Sci, 23(12):(2022) [pubmed]

submitter keyword: mouse, mitochondrial function, MAFLD

isolated hepatocytes

Birgit Knebel
contact affiliation	Institute for Clinical Biochemistry and Pathobiochemistry German Diabetes Center (DDZ) Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf Auf´m Hennekamp 65 40225 Düsseldorf, Germany
contact email	birgit.knebel@ddz.de
lab head
Birgit Knebel
contact affiliation	Institute for Clinical Biochemistry and Pathobiochemistry German Diabetes Center (DDZ) Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
contact email	birgit.knebel@ddz.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/2022/08/PXD032214

PRIDE project URI

• PRIDE
  1. PXD032214
     1. Label: PRIDE project
     2. Name: Adaption of oxidative phosphorylation machinery compensates hepatic lipotoxicity in early stages of MAFLD