PXD040192-2

PXD040192 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial outer membrane integrity regulates a ubiquitin-dependent NF-kB inflammatory response
Description	Mitochondria are often essential for apoptosis through mitochondrial outer membrane permeabilization (MOMP). This central event enables cytochrome c release leading to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory, for instance, causing mitochondrial DNA-dependent activation of cGAS-STING signalling. Alongside having emerging functions in health and disease, MOMP associated inflammation can also elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell counteracts this remain poorly defined. Here, we find that upon MOMP, mitochondria are ubiquitylated in a promiscuous manner targeting proteins localised to both inner and outer mitochondrial membranes. Mitochondrial ubiquitylation serves to recruit the essential adaptor molecule, NEMO, leading to activation of pro-inflammatory NF-kB signalling. We find that disruption of mitochondrial outer membrane integrity through different means leads to engagement of a similar pro-inflammatory signalling platform. Thus, mitochondrial integrity directly controls inflammation, whereby permeabilised mitochondria initiate NF-?B signalling. This may be important for the various pathophysiological functions of MOMP-associated inflammation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:17:51.355.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD040192
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitinylated lysine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 14:03:21	ID requested
1	2023-12-15 08:57:40	announced
⏵ 2	2024-10-22 06:17:51	announced	2024-10-22: Updated project metadata.

10.6019/PXD040192;

submitter keyword: Mitochondria, Apoptosis, NF-?B signaling, Ubiquitin

Sara Rossana Zanivan
contact affiliation	CRUK - Beatson Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040192
     1. Label: PRIDE project
     2. Name: Mitochondrial outer membrane integrity regulates a ubiquitin-dependent NF-kB inflammatory response