SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis

Greene, K. S., Lukey, M. J., Wang, X., Blank, B., Druso, J. E., Lin, M. J., Stalnecker, C. A., Zhang, C., Negron Abril, Y., Erickson, J. W., Wilson, K. F., Lin, H., Weiss, R. S., Cerione, R. A. (December 2019) SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis. Proc Natl Acad Sci U S A. ISSN 1091-6490 (Public Dataset)

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Abstract

The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated during tumorigenesis and is being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, a mitochondrial NAD(+)-dependent lysine deacylase, plays a key role in stabilizing GLS. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating GLS and thereby protecting it from ubiquitin-mediated degradation. Moreover, we show that SIRT5 is up-regulated during cellular transformation and supports proliferation and tumorigenesis. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. These findings reveal a mechanism for increasing GLS expression in cancer cells and establish a role for SIRT5 in metabolic reprogramming and mammary tumorigenesis.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA silencing diseases & disorders > cancer > cancer types > breast cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > organs types and functions > metabolism organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types
CSHL Authors:	Lukey, Michael
Communities:	CSHL labs > Lukey lab
Depositing User:	Adrian Gomez
Date:	16 December 2019
Date Deposited:	27 Jan 2020 16:35
Last Modified:	02 Feb 2024 15:24
PMCID:	PMC6936584
Related URLs:	Publisher
Dataset ID:	Supplement: https://www.pnas.org/content/suppl/2019/12/11/1911954116.DCSupplemental
URI:	https://repository.cshl.edu/id/eprint/38931

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