PXD026045

PXD026045 is an original dataset announced via ProteomeXchange.

Title	Endolysosomal protease leakage reprograms macrophage mitochondrial metabolism
Description	Organelle crosstalk plays important functions in metabolic processes and is relevant to immunity, neurodegeneration, and cancer. The permeabilisation and rupture of endolysosomes during stress can induce inflammation and cell death. There is growing evidence that endomembrane damage does not always result in cell death and that important cellular functions can be regulated by limited endolysosomal damage. However, the effect of limited cytosolic leakage of endolysosomal contents on the function of other cytoplasmic organelles is poorly understood. Here, we show that sterile and non-sterile endolysosomal damage triggers remodelling of the mitochondrial proteome and metabolic reprogramming of human macrophages. Mitochondrial metabolic reprogramming was associated with endolysosomal leakage independently of proteasome degradation and mitophagy. Furthermore, single-cell RNA-sequencing and metabolic analysis of lung macrophages undergoing endomembrane damage showed altered mitochondrial metabolism in mice. We, therefore, uncover an inter-organelle communication mechanism between mitochondria and endolysosomes with limited proteolytic leakage, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprogramming in response to infection or injury.
HostingRepository	PRIDE
AnnounceDate	2022-10-30
AnnouncementXML	Submission_2022-10-30_06:47:06.840.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MatthiasTrost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-17 03:22:13	ID requested
⏵ 1	2022-10-30 06:47:07	announced

Dataset with its publication pending

submitter keyword: Endolysosomal damage, Organelle crosstalk, Proteomics, Mitochondrial metabolic reprogramming

MatthiasTrost
contact affiliation	Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
contact email	matthias.trost@ncl.ac.uk
lab head
MatthiasTrost
contact affiliation	Newcastle University
contact email	matthias.trost@ncl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026045
     1. Label: PRIDE project
     2. Name: Endolysosomal protease leakage reprograms macrophage mitochondrial metabolism