- Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.
Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.
Cell metabolism (2018-08-21)
H Furkan Alkan, Katharina E Walter, Alba Luengo, Corina T Madreiter-Sokolowski, Sarah Stryeck, Allison N Lau, Wael Al-Zoughbi, Caroline A Lewis, Craig J Thomas, Gerald Hoefler, Wolfgang F Graier, Tobias Madl, Matthew G Vander Heiden, Juliane G Bogner-Strauss
PMID30122555
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.
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