Assistant Professor Duke University
Organisms tune their metabolic state to adapt to changes in their environment. Metabolic pathways and intermediary metabolites have emerged as direct regulators of cellular transcription. For example, glucose-derived acetyl-CoA generated from ATP–citrate lyase (ACLY) controls gene expression by modifying histone acetylation. Remarkably, little is known if metabolites other than glucose generate signals to control gene expression. Recently, we’ve identified increases in lipid metabolism lead to potent changes in histone acetylation and gene expression. This work further expands our understanding of how nutrients are sensed, and their signals are integrated into epigenetic control of gene expression.
Hosts: Philipp Gutt and Kei Sakamoto from NIHS
SnapShot: Mammalian Sirtuins. Anderson KA, Green MF, Huynh FK, Wagner GR, Hirschey MD. Cell. 2014 Nov 6;159(4):956-956.e1. doi: 10.1016/j.cell.2014.10.045. PMID: 25417168
Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Wagner GR, Hirschey MD. Mol Cell. 2014 Apr 10;54(1):5-16. doi: 10.1016/j.molcel.2014.03.027. Review. PMID: 24725594
Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, Park J, Chen Y, Huang H, Zhang Y, Ro J, Wagner GR, Green MF, Madsen AS, Schmiesing J, Peterson BS, Xu G, Ilkayeva OR, Muehlbauer MJ, Braulke T, Mühlhausen C, Backos DS, Olsen CA, McGuire PJ, Pletcher SD, Lombard DB, Hirschey MD, Zhao Y. Cell Metab. 2014 Apr 1;19(4):605-17. doi: 10.1016/j.cmet.2014.03.014. PMID: 24703693
Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E. Science. 2013 Jan 11;339(6116):211-4. doi: 10.1126/science.1227166. Epub 2012 Dec 6. PMID: 23223453
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, Stančáková A, Goetzman E, Lam MM, Schwer B, Stevens RD, Muehlbauer MJ, Kakar S, Bass NM, Kuusisto J, Laakso M, Alt FW, Newgard CB, Farese RV Jr, Kahn CR, Verdin E. Mol Cell. 2011 Oct 21;44(2):177-90. doi: 10.1016/j.molcel.2011.07.019.PMID: 21856199
SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E. Cell Metab. 2010 Dec 1;12(6):654-61. doi:10.1016/j.cmet.2010.11.003. PMID: 21109197
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV Jr, Alt FW, Kahn CR, Verdin E. Nature. 2010 Mar 4;464(7285):121-5. doi: 10.1038/nature08778. PMID: 20203611