Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting
Name
emss-80560.pdf
Description
Accepted version
Size
2.71 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Alkan, H. Furkan
Luengo, Alba
Lau, Allison N.
Lewis, Caroline A.
Vander Heiden, Matthew G.
Date Issued
November 2018
Journal
Cell Metabolism
Publisher
Elsevier BV
Citation
Alkan, H. Furkan et al. “Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.” Cell Metabolism 28 (2018): 706-720 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Mitochondrial function is important for aspartate biosynthesis in proliferating cells. Here, we show that mitochondrial aspartate export via the aspartate-glutamate carrier 1 (AGC1) supports cell proliferation and cellular redox homeostasis. Insufficient cytosolic aspartate delivery leads to cell death when TCA cycle carbon is reduced following glutamine withdrawal and/or glutaminase inhibition. Moreover, loss of AGC1 reduces allograft tumor growth that is further compromised by treatment with the glutaminase inhibitor CB-839. Together, these findings argue that mitochondrial aspartate export sustains cell survival in low-glutamine environments and AGC1 inhibition can synergize with glutaminase inhibition to limit tumor growth. Alkan et al. show that, under conditions in which cytosolic glutamine is limiting, mitochondrial aspartate export, via the aspartate-glutamate carrier 1 (AGC1), supports cell proliferation and cellular redox homeostasis and that AGC1 inhibition can synergize with glutaminase inhibition to limit tumor growth.
MIT Department
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cmet.2018.07.021
