PXD005712

PXD005712 is an original dataset announced via ProteomeXchange.

Title	HELA cells PARL Immunoprecipitation part II
Description	Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid-like protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and cell death pathways, but its role in apoptosis remained enigmatic. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac/DIABLO as a PARL substrate. In apoptotic cells, Smac/DIABLO is released into the cytosol and promotes caspase activity by inhibiting IAPs. Intramembrane cleavage of Smac/DIABLO by PARL generates an amino terminal IAP-binding motif, which is required for its apoptotic activity. Loss of PARL impairs proteolytic maturation of Smac/DIABLO, which fails to bind XIAP. Smac/DIABLO peptidomimetics, downregulation of XIAP or cytosolic expression of cleaved Smac/DIABLO restores apoptosis in PARL-deficient cells. Our results discover a pro-apoptotic function of PARL and identify PARL-mediated Smac/DIABLO processing and cytochrome c release facilitated by OPA1 dependent cristae remodeling as two independent pro-apoptotic pathways in mitochondria. Please note that these data are overlapping with data uploaded under: PXD004914. Exclusively in this upload, you will find the S277A mutant immunoprecipitations.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:34:43.832.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-16 03:10:36	ID requested
1	2017-03-01 08:42:15	announced
⏵ 2	2024-10-22 04:34:44	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Human, S277A PARL mutant

Marcus Krüger
contact affiliation	Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany;
contact email	marcus.krueger@uni-koeln.de
lab head
Hendrik Nolte
contact affiliation	Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)
contact email	h.nolte@uni-koeln.de
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/2017/03/PXD005712

PRIDE project URI

• PRIDE
  1. PXD005712
     1. Label: PRIDE project
     2. Name: HELA cells PARL Immunoprecipitation part II