PXD027316

PXD027316 is an original dataset announced via ProteomeXchange.

Title	Sublytic membrane attack complex drives glycolysis and mitochondrial dysfunction with inflammatory consequences in human monocyte-derived macrophages
Description	The terminal stage of the complement activation pathways, the membrane attack complex (MAC), is upregulated in diabetic and rheumatoid arthritis patients, contributing pathologically by increasing inflammation. Previous research has highlighted that a sublytic dose of MAC can initiate NLRP3 inflammasome activation via calcium influx and loss of mitochondrial membrane potential. Here, we show that sublytic concentrations of MAC mediate a previously undescribed perturbation in cellular energy metabolism in human monocyte-derived macrophages, by phenotypic skewing towards glycolysis and upregulation of glycolysis-promoting genes. Sublytic MAC concentrations drive mitochondrial dysfunction, characterised by a fragmented mitochondrial morphology, loss of maximal respiratory response, depleted mitochondrial membrane potential as well as increased mitochondrial reactive oxygen species production. The consequences of these alterations in glycolytic metabolism and mitochondrial dysfunction lead to NLRP3 inflammasome activation, driving gasdermin D formation and IL-18 release. This novel link between sublytic MAC and immunometabolism, with direct consequences for downstream inflammatory processes, is important for development of novel therapeutics for areas where MAC may mediate disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:38:55.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eleanor Dickinson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-14 22:09:17	ID requested
1	2023-03-11 00:03:02	announced
⏵ 2	2023-11-14 08:39:06	announced	2023-11-14: Updated project metadata.

Jimenez-Duran G, Kozole J, Peltier-Heap R, Dickinson ER, Kwiatkowski CR, Zappacosta F, Annan RS, Galwey NW, Nichols EM, Modis LK, Triantafilou M, Triantafilou K, Booty LM, Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages. Front Immunol, 13():918551(2022) [pubmed]

submitter keyword: membrane attack complex, QExactive, glycolysis upregulation, LC-MS/MS

Roland Annan
contact affiliation	Discovery Analytical, GSK, Upper Providence, USA
contact email	Roland.S.Annan@gsk.com
lab head
Eleanor Dickinson
contact affiliation	GlaxoSmithKline
contact email	eleanor.r.dickinson@gmail.com
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/2023/03/PXD027316

PRIDE project URI

• PRIDE
  1. PXD027316
     1. Label: PRIDE project
     2. Name: Sublytic membrane attack complex drives glycolysis and mitochondrial dysfunction with inflammatory consequences in human monocyte-derived macrophages