PXD043212

PXD043212 is an original dataset announced via ProteomeXchange.

Title	Identification of GRAF1 interactome mediated by GRAF1 phosphorylation in response to Mitophagy
Description	Defects in the clearance of dysfunctional mitochondria contribute to the development of heart failure and several neurological disorders including Parkinson’s disease (PD). The mitophagic signaling pathways that control the rapid recognition, ubiquitin-tagging and encasement of dysfunctional mitochondria into protective autophagosomes have been well characterized and a major mechanism involves coordinated control of the serine/threonine kinase PINK1 and the E3 ubiquitin ligase, Parkin. What is less known is how such clearance processes are spatially controlled. Indeed, while recent studies indicate that actin remodeling can facilitate Parkin-dependent mitochondrial clearance, the underlying players that coordinate localized cytoskeletal remodeling to facilitate the trafficking and clearance of damaged mitochondria remain largely unclear. Herein, we demonstrate that the RhoGAP, GRAF1 (Arhgap26), is a PINK1 substrate that controls mitophagy. Cardiomyocyte-restricted GRAF1 depletion led to accumulation of dysfunctional mitochondria and attenuated stress-induced metabolic adaptation in adult hearts. GRAF1 was required for mitochondria release from F-actin anchors, facilitated mitochondria capture by autophagosomes by enhancing Parkin-LC3 interactions, and promoted mitochondria-associated Arp2/3-dependent actin remodeling. This study employs mass spectrometry-based proteomics to elucidate the interactome of GRAF1, focusing on the protein-protein interactions facilitated by GRAF1 phosphorylation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:27:08.040.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine Mills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-22 08:51:03	ID requested
1	2024-01-26 09:43:29	announced
⏵ 2	2024-10-22 06:27:10	announced	2024-10-22: Updated project metadata.

10.1038/s41467-023-43889-6;

Zhu Q, Combs ME, Liu J, Bai X, Wang WB, Herring LE, Liu J, Locasale JW, Bowles DE, Gross RT, Pla MM, Mack CP, Taylor JM, GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis. Nat Commun, 14(1):8187(2023) [pubmed]

submitter keyword: heart, GRAF1, PINK1-Parkin pathway,Mitophagy

Joan Taylor
contact affiliation	Department of Pathology, University of North Carolina at Chapel Hill
contact email	joan_m_taylor@med.unc.edu
lab head
Christine Mills
contact affiliation	University of North Carolina - Chapel Hill
contact email	allie.mills@unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD043212

PRIDE project URI

• PRIDE
  1. PXD043212
     1. Label: PRIDE project
     2. Name: Identification of GRAF1 interactome mediated by GRAF1 phosphorylation in response to Mitophagy