Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism.

Details

Serval ID
serval:BIB_6B0316A28A94
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism.
Journal
Nature communications
Author(s)
Bussi C., Heunis T., Pellegrino E., Bernard E.M., Bah N., Dos Santos M.S., Santucci P., Aylan B., Rodgers A., Fearns A., Mitschke J., Moore C., MacRae J.I., Greco M., Reinheckel T., Trost M., Gutierrez M.G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
28/11/2022
Peer-reviewed
Oui
Volume
13
Number
1
Pages
7338
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Transient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required leakage of lysosomal cathepsins and was independent of mitophagy, mitoproteases and proteasome degradation. In an in vivo mouse model of endomembrane damage, live lung macrophages that internalised crystals displayed impaired mitochondrial function. Single-cell RNA-sequencing revealed that lysosomal damage skewed metabolic and immune responses in alveolar macrophages subsets with increased lysosomal content. Functionally, drug modulation of macrophage metabolism impacted host responses to Mycobacterium tuberculosis infection in an endomembrane damage dependent way. This work uncovers an inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.
Keywords
Animals, Mice, Proteome, Mitochondria, Macrophages, Mitophagy, Peptide Hydrolases, Lysosomes
Pubmed
Open Access
Yes
Create date
05/12/2022 15:18
Last modification date
09/12/2022 6:48
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