PXD045034 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis |
Description | Paracetamol (acetaminophen, APAP) overdose severely damages mitochondria and triggers several apoptotic processes in hepatocytes, but the final outcome is fulminant necrotic cell death, resulting in acute liver failure and mortality. Here, we studied this switch of cell death modes and demonstrate a non-canonical role of the apoptosis-regulating BCL-2 homolog BIM/Bcl2l11 in promoting necrosis by regulating cellular bioenergetics. BIM deficiency enhanced total ATP production and shifted the bioenergetic profile towards glycolysis, resulting in persistent protection from APAP-induced liver injury. Modulation of glucose levels and deletion of mitofusins confirmed that severe APAP toxicity occurs only in cells dependent on oxidative phosphorylation. Glycolytic hepatocytes maintained elevated ATP levels and reduced ROS, which enabled lysosomal recycling of damaged mitochondria by mitophagy. The present study highlights how metabolism and bioenergetics affect drug-induced liver toxicity, and identifies BIM as important regulator of glycolysis, mitochondrial respiration, and oxidative stress signaling. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:59:34.191.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Florian Stengel |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | reagent derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-01 07:48:51 | ID requested | |
1 | 2024-09-24 05:01:55 | announced | |
⏵ 2 | 2024-10-22 06:59:35 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41418-023-01245-7; |
Lambrecht R, Rudolf F, Ü, ckert AK, Sladky VC, Phan TS, Jansen J, Naim S, Kaufmann T, Keogh A, Kirschnek S, Mangerich A, Stengel F, Leist M, Villunger A, Brunner T, Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis. Cell Death Differ, 31(1):119-131(2024) [pubmed] |
Keyword List
submitter keyword: APAP, hepatotoxicity, Paracetamol, necrosis |
Contact List
Florian Stengel |
contact affiliation | Department of Biology, University of Konstanz, Universitaetsstrasse 10, 78457 Konstanz |
contact email | florian.stengel@uni-konstanz.de |
lab head | |
Florian Stengel |
contact affiliation | Universität Konstanz |
contact email | florian.stengel@uni-konstanz.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045034
- Label: PRIDE project
- Name: Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis