Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis. / Hinrichsen, Finn; Hamm, Jacob; Westermann, Magdalena; Schröder, Lena; Shima, Kensuke; Mishra, Neha; Walker, Alesia; Sommer, Nina; Klischies, Kenneth; Prasse, Daniela; Zimmermann, Johannes; Kaiser, Sina; Bordoni, Dora; Fazio, Antonella; Marinos, Georgios; Laue, Georg; Imm, Simon; Tremaroli, Valentina; Basic, Marijana; Häsler, Robert; Schmitz, Ruth A.; Krautwald, Stefan; Wolf, Andrea; Stecher, Bärbel; Schmitt-Kopplin, Philippe; Kaleta, Christoph; Rupp, Jan; Bäckhed, Fredrik; Rosenstiel, Philip; Sommer, Felix.

In: Cell Metabolism, Vol. 33, No. 12, 2021, p. 2355-2366.e8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hinrichsen, F, Hamm, J, Westermann, M, Schröder, L, Shima, K, Mishra, N, Walker, A, Sommer, N, Klischies, K, Prasse, D, Zimmermann, J, Kaiser, S, Bordoni, D, Fazio, A, Marinos, G, Laue, G, Imm, S, Tremaroli, V, Basic, M, Häsler, R, Schmitz, RA, Krautwald, S, Wolf, A, Stecher, B, Schmitt-Kopplin, P, Kaleta, C, Rupp, J, Bäckhed, F, Rosenstiel, P & Sommer, F 2021, 'Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis', Cell Metabolism, vol. 33, no. 12, pp. 2355-2366.e8. https://doi.org/10.1016/j.cmet.2021.11.004

APA

Hinrichsen, F., Hamm, J., Westermann, M., Schröder, L., Shima, K., Mishra, N., Walker, A., Sommer, N., Klischies, K., Prasse, D., Zimmermann, J., Kaiser, S., Bordoni, D., Fazio, A., Marinos, G., Laue, G., Imm, S., Tremaroli, V., Basic, M., ... Sommer, F. (2021). Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis. Cell Metabolism, 33(12), 2355-2366.e8. https://doi.org/10.1016/j.cmet.2021.11.004

Vancouver

Hinrichsen F, Hamm J, Westermann M, Schröder L, Shima K, Mishra N et al. Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis. Cell Metabolism. 2021;33(12):2355-2366.e8. https://doi.org/10.1016/j.cmet.2021.11.004

Author

Hinrichsen, Finn ; Hamm, Jacob ; Westermann, Magdalena ; Schröder, Lena ; Shima, Kensuke ; Mishra, Neha ; Walker, Alesia ; Sommer, Nina ; Klischies, Kenneth ; Prasse, Daniela ; Zimmermann, Johannes ; Kaiser, Sina ; Bordoni, Dora ; Fazio, Antonella ; Marinos, Georgios ; Laue, Georg ; Imm, Simon ; Tremaroli, Valentina ; Basic, Marijana ; Häsler, Robert ; Schmitz, Ruth A. ; Krautwald, Stefan ; Wolf, Andrea ; Stecher, Bärbel ; Schmitt-Kopplin, Philippe ; Kaleta, Christoph ; Rupp, Jan ; Bäckhed, Fredrik ; Rosenstiel, Philip ; Sommer, Felix. / Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis. In: Cell Metabolism. 2021 ; Vol. 33, No. 12. pp. 2355-2366.e8.

Bibtex

@article{46534689a7ac44a88b53d9b1128c9f77,
title = "Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis",
abstract = "Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2ΔIEC). Hk2ΔIEC mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2ΔIEC mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2ΔIEC mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation.",
keywords = "butyrate, hexokinase, HK2, immunometabolism, inflammation, intestinal epithelial cell, microbiota",
author = "Finn Hinrichsen and Jacob Hamm and Magdalena Westermann and Lena Schr{\"o}der and Kensuke Shima and Neha Mishra and Alesia Walker and Nina Sommer and Kenneth Klischies and Daniela Prasse and Johannes Zimmermann and Sina Kaiser and Dora Bordoni and Antonella Fazio and Georgios Marinos and Georg Laue and Simon Imm and Valentina Tremaroli and Marijana Basic and Robert H{\"a}sler and Schmitz, {Ruth A.} and Stefan Krautwald and Andrea Wolf and B{\"a}rbel Stecher and Philippe Schmitt-Kopplin and Christoph Kaleta and Jan Rupp and Fredrik B{\"a}ckhed and Philip Rosenstiel and Felix Sommer",
note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
doi = "10.1016/j.cmet.2021.11.004",
language = "English",
volume = "33",
pages = "2355--2366.e8",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis

AU - Hinrichsen, Finn

AU - Hamm, Jacob

AU - Westermann, Magdalena

AU - Schröder, Lena

AU - Shima, Kensuke

AU - Mishra, Neha

AU - Walker, Alesia

AU - Sommer, Nina

AU - Klischies, Kenneth

AU - Prasse, Daniela

AU - Zimmermann, Johannes

AU - Kaiser, Sina

AU - Bordoni, Dora

AU - Fazio, Antonella

AU - Marinos, Georgios

AU - Laue, Georg

AU - Imm, Simon

AU - Tremaroli, Valentina

AU - Basic, Marijana

AU - Häsler, Robert

AU - Schmitz, Ruth A.

AU - Krautwald, Stefan

AU - Wolf, Andrea

AU - Stecher, Bärbel

AU - Schmitt-Kopplin, Philippe

AU - Kaleta, Christoph

AU - Rupp, Jan

AU - Bäckhed, Fredrik

AU - Rosenstiel, Philip

AU - Sommer, Felix

N1 - Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021

Y1 - 2021

N2 - Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2ΔIEC). Hk2ΔIEC mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2ΔIEC mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2ΔIEC mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation.

AB - Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2ΔIEC). Hk2ΔIEC mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2ΔIEC mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2ΔIEC mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation.

KW - butyrate

KW - hexokinase

KW - HK2

KW - immunometabolism

KW - inflammation

KW - intestinal epithelial cell

KW - microbiota

U2 - 10.1016/j.cmet.2021.11.004

DO - 10.1016/j.cmet.2021.11.004

M3 - Journal article

C2 - 34847376

AN - SCOPUS:85120446938

VL - 33

SP - 2355-2366.e8

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 12

ER -

ID: 286999905