PXD037797-1

PXD037797 is an original dataset announced via ProteomeXchange.

Title	PARK15/FBXO7 is dispensable for PINK1/Parkin mitophagy in iNeurons and HeLa cell systems
Description	The protein kinase PINK1 and ubiquitin ligase Parkin promote removal of damaged mitochondria via a feed-forward mechanism involving ubiquitin (Ub) phosphorylation (pUb), Parkin activation, and ubiquitylation of mitochondrial outer membrane proteins to support recruitment of mitophagy receptors. The ubiquitin ligase substrate receptor FBXO7/PARK15 is mutated in an early-onset parkinsonian-pyramidal syndrome. Previous studies have proposed a role for FBXO7 in promoting Parkin-dependent mitophagy. Here, we systematically examine the involvement of FBXO7 in depolarization and mtUPR-dependent mitophagy in the well-established HeLa and induced-neurons cell systems. We find that FBXO7-/- cells have no demonstrable defect in: 1) kinetics of pUb accumulation, 2) pUb puncta on mitochondria by super-resolution imaging, 3) recruitment of Parkin and autophagy machinery to damaged mitochondria, 4) mitophagic flux, and 5) mitochondrial clearance as quantified by global proteomics. Moreover, global proteomics of neurogenesis in the absence of FBXO7 reveals no obvious alterations in mitochondria or other organelles. These results argue against a general role for FBXO7 in Parkin-dependent mitophagy and point to the need for additional studies to define how FBXO7 mutations promote parkinsonian-pyramidal syndrome.
HostingRepository	PRIDE
AnnounceDate	2023-06-19
AnnouncementXML	Submission_2023-06-19_05:08:35.574.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	FelixKraus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-28 07:19:17	ID requested
⏵ 1	2023-06-19 05:08:35	announced
2	2023-11-14 06:44:26	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:48:41	announced	2024-10-22: Updated project metadata.

submitter keyword: mitophagy, proteomics, iNeurons,FBXO7

J. WadeHarper
contact affiliation	Department of Cell Biology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave, Boston MA 02115, USA Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
contact email	wade_harper@hms.harvard.edu
lab head
FelixKraus
contact affiliation	Harvard Medical Sschool
contact email	felix_kraus@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037797
     1. Label: PRIDE project
     2. Name: PARK15/FBXO7 is dispensable for PINK1/Parkin mitophagy in iNeurons and HeLa cell systems