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PXD056956-1

PXD056956 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOpposing roles for AMPK in regulating distinct mitophagy pathways
DescriptionMitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. While AMPK, the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear. We found that AMPK directly inhibits NIX-dependent mitophagy by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 and an additional identified site, Ser694. In contrast, AMPK activation increases Parkin phosphorylation and enhances the rate of depolarisation-induced mitophagy, independently of ULK1. We show that this happens both in cultured cells and tissues in vivo, using the mito-QC mouse model. Our work unveils a mechanism whereby AMPK activation downregulates mitophagy of functional mitochondria but enhances that of dysfunctional/damaged ones.
HostingRepositoryPRIDE
AnnounceDate2024-11-29
AnnouncementXMLSubmission_2024-11-29_02:18:00.185.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRenata Soares
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentLTQ Orbitrap Velos; Orbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-18 10:06:39ID requested
12024-11-29 02:18:00announced
Publication List
10.1016/J.MOLCEL.2024.10.025;
Keyword List
submitter keyword: autophagy, NIX, Parkin, skeletal muscle, liver,AMPK, ULK, mitophagy
Contact List
Ian G. Ganley
contact affiliationMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
contact emaili.ganley@dundee.ac.uk
lab head
Renata Soares
contact affiliationMRC-PPU, University of Dundee
contact emailr.filipesoares@dundee.ac.uk
dataset submitter
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Dataset FTP location
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