PXD053221
PXD053221 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: APAP, AILI, NAE1, NEDD8 |
Contact List
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 |
Full Dataset Link List
iProX dataset URI |