Reference : PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains T(reg) homeostasis ...
Scientific journals : Article
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/53971
PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains T(reg) homeostasis during ageing.
English
Danileviciute, Egle [> >]
Zeng, Ni [> >]
Capelle, Christophe M. [> >]
Paczia, Nicole [> >]
Gillespie, Mark A. [> >]
Kurniawan, Henry mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology]
Benzarti, Mohaned [> >]
Merz, Myriam P. [> >]
Coowar, Djalil mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services]
Fritah, Sabrina [> >]
Vogt Weisenhorn, Daniela Maria [> >]
Gomez Giro, Gemma mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology]
Grusdat, Melanie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics]
Baron, Alexandre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Guerin, Coralie [> >]
Franchina, Davide G. [> >]
Léonard, Cathy [> >]
Domingues, Olivia [> >]
Delhalle, Sylvie [> >]
Wurst, Wolfgang [> >]
Turner, Jonathan mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
Schwamborn, Jens Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology]
Meiser, Johannes mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Krüger, Rejko mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Ranish, Jeff [> >]
Brenner, Dirk mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics]
Linster, Carole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Enzymology and Metabolism]
Balling, Rudi [> >]
Ollert, Markus mailto [University of Luxembourg > >]
He, Feng mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
26-May-2022
Nature metabolism
4
5
589-607
Yes
International
2522-5812
2522-5812
Germany
[en] Aging ; Animals ; Homeostasis ; Mice ; Oxidoreductases/metabolism ; Parkinson Disease/enzymology/genetics/metabolism ; Protein Deglycase DJ-1/genetics ; Pyruvates/metabolism ; T-Lymphocytes, Regulatory/metabolism
[en] 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 (T(reg) 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 T(reg) survival starting in young mice and reduces T(reg) 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 T(reg) 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 T(reg) homeostasis is dysregulated in many complex diseases, the DJ-1-PDHB axis represents a potential target to maintain or re-establish T(reg) homeostasis.
http://hdl.handle.net/10993/53971
10.1038/s42255-022-00576-y
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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