RT Journal Article
T1 Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis
A1 Bodineau, Clément
A1 Tomé, Mercedes
A1 Courtois, Sarah
A1 Costa, Ana S H.
A1 Sciacovelli, Marco
A1 Rousseau, Benoit
A1 Richard, Elodie
A1 Vacher, Pierre
A1 Parejo-Pérez, Carlos
A1 Bessede, Emilie
A1 Varon, Christine
A1 Soubeyran, Pierre
A1 Frezza, Christian
A1 Murdoch, Piedad Del Socorro
A1 Villar, Victor H.
A1 Durán, Raúl V.
K1 Asparagine
K1 Cell death
K1 Cells
K1 Glutamine
K1 Growth
K1 Rôle
K1 Signal transduction
K1 Asparagina
K1 Muerte celular
K1 Células
K1 Glutamina
K1 Crecimiento
K1 Rol
K1 Transducción de señales
AB Glutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer.
PB Springer Nature
YR 2021
FD 2021-08-10
LK http://hdl.handle.net/10668/3934
UL http://hdl.handle.net/10668/3934
LA en
NO Bodineau C, Tomé M, Courtois S, Costa ASH, Sciacovelli M, Rousseau B, et al. Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nat Commun. 2021 Aug 10;12(1):4814
DS RISalud
RD Apr 7, 2025