Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation

doi:10.1016/j.celrep.2021.109487

	Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation
	Koronowski, Kevin B.2; Greco, Carolina M.2; Huang, He 1,3; Kim, Jin-Kwang 4; Fribourgh, Jennifer L.5,6; Crosby, Priya 5,6; Mathur, Lavina 2; Ren, Xuelian 1; Partch, Carrie L.5,6; Jang, Cholsoon 2
刊名	CELL REPORTS
	2021-08-03
卷号	36 期号:5 页码:17
ISSN号	2211-1247
DOI	10.1016/j.celrep.2021.109487
通讯作者	Koronowski, Kevin B.(kkoronow@hs.uci.edu) ; Greco, Carolina M.(grecoc@hs.uci.edu)
英文摘要	Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. beta-hydroxybutyrate (beta-OHB) is utilized in lysine beta-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tissue-specific manner by a variety of interventions that evoke beta-OHB. Mass spectrometry analysis of the beta-hydroxybutyrylome in mouse liver revealed 891 sites of Kbhb within 267 proteins enriched for fatty acid, amino acid, detoxification, and one-carbon metabolic pathways. Kbhb inhibits S-adenosyl-L-homocysteine hydrolase (AHCY), a rate-limiting enzyme of the methionine cycle, in parallel with altered metabolite levels. Our results illuminate the role of Kbhb in hepatic metabolism under ketogenic conditions and demonstrate a functional consequence of this modification on a central metabolic enzyme.
资助项目	NIH[R01GM115961] ; NIH[R01DK107868] ; NIH[R01DK118266] ; NIH[R21DK114652] ; NIH[R21AG053592] ; Novo Nordisk Foundation[NNF-202585] ; NIH-NINDS[T32 5T32NS045540] ; NIH-NINDS[F32DK121425] ; National Cancer Institute of the U.S. National Institutes of Health[NIH T32 2T32CA009054-36A1] ; European Research Council[ERC MSCA-IF-2016 MetEpiClock 749869]
WOS关键词	S-ADENOSYLHOMOCYSTEINE HYDROLASE ; HISTONE ACETYLATION ; FUEL METABOLISM ; GENE-EXPRESSION ; KETONE-BODIES ; PROTEIN ; DIET ; IDENTIFICATION ; TRANSCRIPTION ; EPIGENETICS
WOS研究方向	Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000681653300022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298153]
专题	中国科学院上海药物研究所
通讯作者	Koronowski, Kevin B.; Greco, Carolina M.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Calif Irvine, Ctr Epigenet & Metab, U1233 INSERM, Dept Biol Chem, Irvine, CA 92697 USA 3.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA 4.Univ Calif Irvine, Dept Biol Chem, Irvine Sch Med, Irvine, CA 92697 USA 5.Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA 6.Univ Calif San Diego, Ctr Circadian Biol, La Jolla, CA 92093 USA
推荐引用方式 GB/T 7714	Koronowski, Kevin B.,Greco, Carolina M.,Huang, He,et al. Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation[J]. CELL REPORTS,2021,36(5):17.
APA	Koronowski, Kevin B..,Greco, Carolina M..,Huang, He.,Kim, Jin-Kwang.,Fribourgh, Jennifer L..,...&Sassone-Corsi, Paolo.(2021).Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation.CELL REPORTS,36(5),17.
MLA	Koronowski, Kevin B.,et al."Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation".CELL REPORTS 36.5(2021):17.