PXD053221

PXD053221 is an original dataset announced via ProteomeXchange.

Title	Neddylation inhibition halts acetaminophen induced liver injury boosting anabolic cardiolipin pathway
Description	Drug Induced-liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. APAP overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Herein, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from APAP-induced liver injury (AILI) patients and in mice treated with an APAP overdose. MLN4924, an inhibitor of the NEDD8 activating enzyme (NAE-1), ameliorated necrosis and boost liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 (bioNEDD8) and Ubiquitin (bioUB) transgenic mice were investigated under APAP overdose with and without MLN4924. The CDP-DAG synthase TAM41, responsible to produce cardiolipin essential for mitochondrial activity, was found modulated under AILI and restoring its levels by inhibiting neddylation. Understanding this ubiquitin-like crosstalk in AILI is essential for developing promising targeted inhibitors for DILI treatment.
HostingRepository	iProX
AnnounceDate	2024-06-18
AnnouncementXML	Submission_2024-12-12_19:07:17.144.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-18 21:58:00	ID requested
1	2024-06-18 22:00:59	announced
⏵ 2	2024-12-12 19:07:18	announced	2024-12-13: Update information.

Gil-Pitarch C, Serrano-Maci, á M, Simon J, Mosca L, Conter C, Rejano-Gordillo CM, Zapata-Pavas LE, Pe, ñ, a-Sanf, é, lix P, Azkargorta M, Rodr, í, guez-Agudo R, Lachiondo-Ortega S, Mercado-G, ó, mez M, Delgado TC, Porcelli M, Aurrekoetxea I, Sutherland JD, Barrio R, Xirodimas D, Aspichueta P, Elortza F, Mart, í, nez-Cruz LA, Nogueiras R, Iruzubieta P, Crespo J, Masson S, McCain MV, Reeves HL, Andrade RJ, Lucena MI, Mayor U, Goikoetxea-Usandizaga N, Gonz, á, lez-Recio I, Mart, í, nez-Chantar ML, Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway. Cell Rep Med, 5(7):101653(2024) [pubmed]

submitter keyword: APAP, AILI, NAE1, NEDD8

Felix Elortza
contact affiliation	Center for Cooperative Research in Biosciences (CIC bioGUNE）
contact email	felortza@cicbogune.es
lab head
Mikel Azkargorta
contact affiliation	Center for Cooperative Research in Biosciences (CIC bioGUNE）
contact email	mazkargorta@cicbiogune.es
dataset submitter

iProX dataset URI