A variant of SLC1A5 is a mitochondrial glutamine transporter for metabolic reprogramming in cancer cells

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Title
A variant of SLC1A5 is a mitochondrial glutamine transporter for metabolic reprogramming in cancer cells
Author(s)
H C Yoo; S J Park; M Nam; J Kang; K Kim; J H Yeo; J K Kim; Y Heo; H S Lee; Myeong Youl LeeChang Woo LeeJong Soon Kang; Y H Kim; J Lee; J Choi; G S Hwang; S Bang; J M Han
Bibliographic Citation
Cell Metabolism, vol. 31, pp. 267-283
Publication Year
2020
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.
Keyword
ASCT2HIF-2αSLC1A5SLC1A5 variantcancer metabolismgemcitabine resistanceglutaminehypoxiametabolic reprogrammingmitochondrial glutamine transporter
ISSN
1550-4131
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.cmet.2019.11.020
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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