UNIGE document Scientific Article
previous document  unige:145494  next document
add to browser collection
Title

Macrophage-derived glutamine boosts satellite cells and muscle regeneration

Authors
Shang, Min
Cappellesso, Federica
Amorim, Ricardo
Serneels, Jens
Virga, Federico
Eelen, Guy
Rincon, Melvin Y.
show hidden authors show all authors [1 - 17]
Published in Nature. 2020, vol. 587, no. 7835, p. 626-631
Abstract Muscle regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells. Macrophages and satellite cells communicate in different ways, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and muscle regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the regeneration of injured or aged muscles.
Identifiers
PMID: 33116312
Full text
Article (Published version) (11.6 MB) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.nature.com/articles/s41586-020-2857-9
Structures
Research group Mitochondries et métabolisme énergétique (671)
Citation
(ISO format)
SHANG, Min et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration. In: Nature, 2020, vol. 587, n° 7835, p. 626-631. doi: 10.1038/s41586-020-2857-9 https://archive-ouverte.unige.ch/unige:145494

147 hits

1 download

Update

Deposited on : 2020-11-30

Export document
Format :
Citation style :