Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner

Yun-Qian Wang, Hao-Lian Wang, Jie Xu, Juan Tan, Lin-Na Fu, Ji-Lin Wang, Tian-Hui Zou, Dan-Feng Sun, Qin-Yan Gao, Ying-Xuan Chen () and Jing-Yuan Fang
Additional contact information
Yun-Qian Wang: Shanghai Jiao Tong University
Hao-Lian Wang: Shanghai Jiao Tong University
Jie Xu: Shanghai Jiao Tong University
Juan Tan: Shanghai Jiao Tong University
Lin-Na Fu: Shanghai Jiao Tong University
Ji-Lin Wang: Shanghai Jiao Tong University
Tian-Hui Zou: Shanghai Jiao Tong University
Dan-Feng Sun: Shanghai Jiao Tong University
Qin-Yan Gao: Shanghai Jiao Tong University
Ying-Xuan Chen: Shanghai Jiao Tong University
Jing-Yuan Fang: Shanghai Jiao Tong University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-02951-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02951-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-02951-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().