Cytosolic Aspartate Availability Determines Cell Survival When Glutamine Is Limiting.
Cell Metab
; 28(5): 706-720.e6, 2018 11 06.
Article
em 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.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sobrevivência Celular
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Ácido Aspártico
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Antiporters
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Sistemas de Transporte de Aminoácidos Acídicos
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Citosol
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Glutamina
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article