期刊
CELL METABOLISM
卷 31, 期 2, 页码 267-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2019.11.020
关键词
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资金
- Global Ph.D. Fellowship Program [NRF-2015H1A2A1031134]
- Global Frontier Project Grant [NRF-2013M3A6A4072536]
- National Research Foundation of Korea - Ministry of Education [2018R1A6A1A03023718]
- Korea Basic Science Institute [T39720]
- National Research Council of Science & Technology (NST), Republic of Korea [T39720, C060200] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2018R1A6A1A03023718] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 mitochondria! localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2 alpha. 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.
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