Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression

Gloria Asantewaa; Emily T. Tuttle; Nathan P. Ward; Yun Pyo Kang; Yumi Kim; Madeline E. Kavanagh; Nomeda Girnius; Ying Chen; Katherine Rodriguez; Fabio Hecht; Marco Zocchi; Leonid Smorodintsev-Schiller; Tash Jaé Q. Scales; Kira Taylor; Fatemeh Alimohammadi; Renae P. Duncan; Zachary R. Sechrist; Diana Agostini-Vulaj; Xenia L. Schafer; Hayley Chang; Zachary R. Smith; Thomas N. O’Connor; Sarah Whelan; Laura M. Selfors; Jett Crowdis; G. Kenneth Gray; Roderick T. Bronson; Dirk Brenner; Alessandro Rufini; Robert T. Dirksen; Aram F. Hezel; Aaron R. Huber; Joshua Munger; Benjamin F. Cravatt; Vasilis Vasiliou; Calvin L. Cole; Gina M. DeNicola; Isaac S. Harris

doi:10.1038/s41467-024-50454-2

Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression

Gloria Asantewaa, Emily T. Tuttle, Nathan P. Ward, Yun Pyo Kang, Yumi Kim, Madeline E. Kavanagh, Nomeda Girnius, Ying Chen, Katherine Rodriguez, Fabio Hecht, Marco Zocchi, Leonid Smorodintsev-Schiller, Tash Jaé Q. Scales, Kira Taylor, Fatemeh Alimohammadi, Renae P. Duncan, Zachary R. Sechrist, Diana Agostini-Vulaj, Xenia L. Schafer, Hayley ChangZachary R. Smith, Thomas N. O’Connor, Sarah Whelan, Laura M. Selfors, Jett Crowdis, G. Kenneth Gray, Roderick T. Bronson, Dirk Brenner, Alessandro Rufini, Robert T. Dirksen, Aram F. Hezel, Aaron R. Huber, Joshua Munger, Benjamin F. Cravatt, Vasilis Vasiliou, Calvin L. Cole, Gina M. DeNicola, Isaac S. Harris^*

^*Corresponding author for this work

Experimental and Molecular Immunology

Research output: Contribution to journal › Article › Research › peer-review

Abstract

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Original language	English
Article number	6152
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-50454-2
Publication status	Published - 21 Jul 2024

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Asantewaa, G., Tuttle, E. T., Ward, N. P., Kang, Y. P., Kim, Y., Kavanagh, M. E., Girnius, N., Chen, Y., Rodriguez, K., Hecht, F., Zocchi, M., Smorodintsev-Schiller, L., Scales, T. J. Q., Taylor, K., Alimohammadi, F., Duncan, R. P., Sechrist, Z. R., Agostini-Vulaj, D., Schafer, X. L., ... Harris, I. S. (2024). Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nature Communications, 15(1), Article 6152. https://doi.org/10.1038/s41467-024-50454-2

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title = "Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression",

abstract = "Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.",

author = "Gloria Asantewaa and Tuttle, {Emily T.} and Ward, {Nathan P.} and Kang, {Yun Pyo} and Yumi Kim and Kavanagh, {Madeline E.} and Nomeda Girnius and Ying Chen and Katherine Rodriguez and Fabio Hecht and Marco Zocchi and Leonid Smorodintsev-Schiller and Scales, {Tash Ja{\'e} Q.} and Kira Taylor and Fatemeh Alimohammadi and Duncan, {Renae P.} and Sechrist, {Zachary R.} and Diana Agostini-Vulaj and Schafer, {Xenia L.} and Hayley Chang and Smith, {Zachary R.} and O{\textquoteright}Connor, {Thomas N.} and Sarah Whelan and Selfors, {Laura M.} and Jett Crowdis and Gray, {G. Kenneth} and Bronson, {Roderick T.} and Dirk Brenner and Alessandro Rufini and Dirksen, {Robert T.} and Hezel, {Aram F.} and Huber, {Aaron R.} and Joshua Munger and Cravatt, {Benjamin F.} and Vasilis Vasiliou and Cole, {Calvin L.} and DeNicola, {Gina M.} and Harris, {Isaac S.}",

note = "Acknowledgements We thank Jonathan Coloff and Samuel McBrayer for their feedback and discussions. We would also like to thank the Genomics Research Center (GRC), the Histology, Biochemistry, and Molecular Imaging (HBMI) Core at the Center for Musculoskeletal Research (CMSR), and the Center for Advanced Research Technologies (CART) at URMC, the Bauer Core Facility at Harvard University, and Proteomics/Metabolomics Core at Moffitt Cancer Center, which is funded in part by Moffitt{\textquoteright}s Cancer Center Support Grant (P30CA076292). We also thank Joan Brugge and the Ludwig Cancer Center at Harvard Medical School for their support. This work was supported by the Wilmot Cancer Institute Predoctoral Fellowship (G.A.), Wilmot Cancer Institute Pilot Funding (I.S.H.), the Amer ican Association for Cancer Research and Breast Cancer Research Foundation (20-20-26-HARR) (I.S.H.), Breast Cancer Coalition of Rochester (I.S.H.), a Sir Henry Wellcome Postdoctoral Fellowship (M.E.K.), and a FNR-CORE grant C21/BM/15796788 (D.B.), and NIH grants R01CA269813 (I.S.H.), R37CA230042 (G.M.D), R24AA022057 (V.V.), R01AA028859 (Y.C.), AI150698 (J.M.), K01CA240533-01A1 (C.L.C.), and R01AR078000 (R.T.D.). Schematics in Figs. 1A, 2I, 4A, 5A, and 6A were created with BioRender.com. Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jul,

day = "21",

doi = "10.1038/s41467-024-50454-2",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Asantewaa, G, Tuttle, ET, Ward, NP, Kang, YP, Kim, Y, Kavanagh, ME, Girnius, N, Chen, Y, Rodriguez, K, Hecht, F, Zocchi, M, Smorodintsev-Schiller, L, Scales, TJQ, Taylor, K, Alimohammadi, F, Duncan, RP, Sechrist, ZR, Agostini-Vulaj, D, Schafer, XL, Chang, H, Smith, ZR, O’Connor, TN, Whelan, S, Selfors, LM, Crowdis, J, Gray, GK, Bronson, RT, Brenner, D, Rufini, A, Dirksen, RT, Hezel, AF, Huber, AR, Munger, J, Cravatt, BF, Vasiliou, V, Cole, CL, DeNicola, GM & Harris, IS 2024, 'Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression', Nature Communications, vol. 15, no. 1, 6152. https://doi.org/10.1038/s41467-024-50454-2

TY - JOUR

T1 - Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression

AU - Asantewaa, Gloria

AU - Tuttle, Emily T.

AU - Ward, Nathan P.

AU - Kang, Yun Pyo

AU - Kim, Yumi

AU - Kavanagh, Madeline E.

AU - Girnius, Nomeda

AU - Chen, Ying

AU - Rodriguez, Katherine

AU - Hecht, Fabio

AU - Zocchi, Marco

AU - Smorodintsev-Schiller, Leonid

AU - Scales, Tash Jaé Q.

AU - Taylor, Kira

AU - Alimohammadi, Fatemeh

AU - Duncan, Renae P.

AU - Sechrist, Zachary R.

AU - Agostini-Vulaj, Diana

AU - Schafer, Xenia L.

AU - Chang, Hayley

AU - Smith, Zachary R.

AU - O’Connor, Thomas N.

AU - Whelan, Sarah

AU - Selfors, Laura M.

AU - Crowdis, Jett

AU - Gray, G. Kenneth

AU - Bronson, Roderick T.

AU - Brenner, Dirk

AU - Rufini, Alessandro

AU - Dirksen, Robert T.

AU - Hezel, Aram F.

AU - Huber, Aaron R.

AU - Munger, Joshua

AU - Cravatt, Benjamin F.

AU - Vasiliou, Vasilis

AU - Cole, Calvin L.

AU - DeNicola, Gina M.

AU - Harris, Isaac S.

N1 - Acknowledgements We thank Jonathan Coloff and Samuel McBrayer for their feedback and discussions. We would also like to thank the Genomics Research Center (GRC), the Histology, Biochemistry, and Molecular Imaging (HBMI) Core at the Center for Musculoskeletal Research (CMSR), and the Center for Advanced Research Technologies (CART) at URMC, the Bauer Core Facility at Harvard University, and Proteomics/Metabolomics Core at Moffitt Cancer Center, which is funded in part by Moffitt’s Cancer Center Support Grant (P30CA076292). We also thank Joan Brugge and the Ludwig Cancer Center at Harvard Medical School for their support. This work was supported by the Wilmot Cancer Institute Predoctoral Fellowship (G.A.), Wilmot Cancer Institute Pilot Funding (I.S.H.), the Amer ican Association for Cancer Research and Breast Cancer Research Foundation (20-20-26-HARR) (I.S.H.), Breast Cancer Coalition of Rochester (I.S.H.), a Sir Henry Wellcome Postdoctoral Fellowship (M.E.K.), and a FNR-CORE grant C21/BM/15796788 (D.B.), and NIH grants R01CA269813 (I.S.H.), R37CA230042 (G.M.D), R24AA022057 (V.V.), R01AA028859 (Y.C.), AI150698 (J.M.), K01CA240533-01A1 (C.L.C.), and R01AR078000 (R.T.D.). Schematics in Figs. 1A, 2I, 4A, 5A, and 6A were created with BioRender.com. Publisher Copyright: © The Author(s) 2024.

PY - 2024/7/21

Y1 - 2024/7/21

N2 - Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

AB - Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

UR - http://www.scopus.com/inward/record.url?scp=85199216942&partnerID=8YFLogxK

UR - https://pubmed.ncbi.nlm.nih.gov/39034312

U2 - 10.1038/s41467-024-50454-2

DO - 10.1038/s41467-024-50454-2

M3 - Article

C2 - 39034312

AN - SCOPUS:85199216942

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6152

ER -

Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression

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