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Danileviciute, E.* ; Zeng, N.* ; Capelle, C.M.* ; Paczia, N.* ; Gillespie, M.A.* ; Kurniawan, H.* ; Benzarti, M.* ; Merz, M.P.* ; Coowar, D.* ; Fritah, S.* ; Vogt Weisenhorn, D.M. ; Gomez Giro, G.* ; Grusdat, M.* ; Baron, A.* ; Guerin, C.* ; Franchina, D.G.* ; Leonard, C.* ; Domingues, O.* ; Delhalle, S.* ; Wurst, W. ; Turner, J.D.* ; Schwamborn, J.C.* ; Meiser, J.* ; Krüger, R.* ; Ranish, J.* ; Brenner, D.* ; Linster, C.L.* ; Balling, R.* ; Ollert, M.* ; Hefeng, F.Q.*

PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing.

Nat. Metab. 4, 589-607 (2022)
Postprint DOI PMC
Open Access Green
Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson’s disease gene) is a pacemaker regulating PDH activity in CD4+ regulatory T cells (Treg cells). DJ-1 binds to PDHE1-β (PDHB), inhibiting phosphorylation of PDHE1-α (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Park7 (Dj-1) deletion impairs Treg survival starting in young mice and reduces Treg homeostatic proliferation and cellularity only in aged mice. This leads to increased severity in aged mice during the remission of experimental autoimmune encephalomyelitis (EAE). Dj-1 deletion also compromises differentiation of inducible Treg cells especially in aged mice, and the impairment occurs via regulation of PDHB. These findings provide unforeseen insight into the complicated regulatory machinery of the PDH complex. As Treg homeostasis is dysregulated in many complex diseases, the DJ-1–PDHB axis represents a potential target to maintain or re-establish Treg homeostasis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Journal Nature metabolism
Quellenangaben Volume: 4, Issue: 5, Pages: 589-607 Article Number: , Supplement: ,
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Grants Fonds national de la Recherche Luxembourg
Deutsche Forschungsgemeinschaft