AI Article Synopsis
- - Glutamoptosis refers to cell death triggered by irregular glutaminolysis and mTORC1 signaling during nutrient imbalances, particularly in rapidly dividing cells.
- - The study reveals that reactivating AMPK can block the mTORC1 activation linked to glutamine and prevent glutamoptosis in both lab and live models.
- - Research demonstrates that glutamine not only supports energy production via asparagine synthesis and the GABA pathway but also interacts with mTORC1 through two key pathways, emphasizing its potential role in therapy for diseases like cancer.
Article Abstract
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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355106 | PMC |
| http://dx.doi.org/10.1038/s41467-021-25079-4 | DOI Listing |
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