PXD056956

PXD056956 is an original dataset announced via ProteomeXchange.

Title	Opposing roles for AMPK in regulating distinct mitophagy pathways
Description	Mitophagy 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.
HostingRepository	PRIDE
AnnounceDate	2024-11-29
AnnouncementXML	Submission_2024-11-29_02:18:00.185.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Renata Soares
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-18 10:06:39	ID requested
⏵ 1	2024-11-29 02:18:00	announced

10.1016/J.MOLCEL.2024.10.025;

submitter keyword: autophagy, NIX, Parkin, skeletal muscle, liver,AMPK, ULK, mitophagy

Ian G. Ganley
contact affiliation	MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K.
contact email	i.ganley@dundee.ac.uk
lab head
Renata Soares
contact affiliation	MRC-PPU, University of Dundee
contact email	r.filipesoares@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056956
     1. Label: PRIDE project
     2. Name: Opposing roles for AMPK in regulating distinct mitophagy pathways