Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.
Cell Metab
; 28(5): 706-720.e6, 2018 11 06.
Article
in En
| MEDLINE
| ID: mdl-30122555
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Survival
/
Aspartic Acid
/
Antiporters
/
Amino Acid Transport Systems, Acidic
/
Cytosol
/
Glutamine
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2018
Type:
Article
Affiliation country:
United States