PXD045621

PXD045621 is an original dataset announced via ProteomeXchange.

Title	Insulin signaling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons
Description	Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization of PTEN-induced kinase 1 (PINK1) requires transport of Pink1 mRNA by tethering it to the mitochondrial surface. Here, we report that inhibition of AMPK by activation of the insulin signaling cascade prevents Pink1 mRNA binding to mitochondria. Mechanistically, AMPK phosphorylates the RNA anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site that is necessary for its interaction with the RNA-binding protein SYNJ2. Interestingly, loss of mitochondrial Pink1 mRNA association upon insulin addition is required for PINK1 protein activation and its function as a ubiquitin kinase in the mitophagy pathway, thus placing PINK1 function under metabolic control. Induction of insulin-resistance in vitro by the key genetic Alzheimer-risk factor apolipoprotein E4 retains Pink1 mRNA at the mitochondria and prevents proper PINK1 activity especially in neurites. Our results thus identify a metabolic switch controlling Pink1 mRNA localization and PINK1 activity via insulin and AMPK signaling in neurons and propose a mechanistic connection between insulin resistance and mitochondrial dysfunction.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:31:33.471.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-24 03:07:18	ID requested
1	2024-02-23 08:53:42	announced
⏵ 2	2024-10-22 06:31:33	announced	2024-10-22: Updated project metadata.

10.1038/S42255-024-01007-W;

submitter keyword: neurons,mitochondria, AMPK, SYNJ2BP, phosphoproteomics, insulin

Prof. Angelika Harbauer
contact affiliation	Max Planck Institute for Biological Intelligence, Martinsried, Germany Technical University of Munich, Institute of Neuronal Cell Biology, Munich, Germany Munich Cluster for Systems Neurology, Munich, Germany
contact email	angelika.harbauer@bi.mpg.de
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045621
     1. Label: PRIDE project
     2. Name: Insulin signaling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons