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A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells

Authors
 Hee Chan Yoo  ;  Seung Joon Park  ;  Miso Nam  ;  Juwon Kang  ;  Kibum Kim  ;  Joo Hye Yeo  ;  Joon-Ki Kim  ;  Yunkyung Heo  ;  Hee Seung Lee  ;  Myeong Youl Lee  ;  Chang Woo Lee  ;  Jong Soon Kang  ;  Yun-Hee Kim  ;  Jinu Lee  ;  Junjeong Choi  ;  Geum-Sook Hwang  ;  Seungmin Bang  ;  Jung Min Han 
Citation
 CELL METABOLISM, Vol.31(2) : 267-283.e12, 2020 
Journal Title
 CELL METABOLISM 
ISSN
 1550-4131 
Issue Date
2020
Keywords
ASCT2 ; HIF-2α ; SLC1A5 ; SLC1A5 variant ; cancer metabolism ; gemcitabine resistance ; glutamine ; hypoxia ; metabolic reprogramming ; mitochondrial glutamine transporter
Abstract
Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays a critical role in cancer metabolic reprogramming by transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminal targeting signal for mitochondrial localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediates glutamine-induced ATP production and glutathione synthesis and confers gemcitabine resistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpression alter cancer cell and tumor growth, supporting an oncogenic role. This work demonstrates that the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolic reprogramming.
Full Text
https://www.sciencedirect.com/science/article/pii/S1550413119306643
DOI
10.1016/j.cmet.2019.11.020
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175172
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