Department of Genetics, Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Autophagy. 2022 Nov;18(11):2749-2750. doi: 10.1080/15548627.2022.2062875. Epub 2022 Apr 26.
Cancer cells metabolize glutamine mostly through glutaminolysis, a metabolic pathway that activates MTORC1. The AMPK-MTORC1 signaling axis is a key regulator of cell growth and proliferation. Our recent investigation identified that the connection between glutamine and AMPK is not restricted to glutaminolysis. Rather, we demonstrated the crucial role of ASNS (asparagine synthetase (glutamine-hydrolyzing)) and the GABA shunt for the metabolic control of the AMPK-MTORC1 axis during glutamine sufficiency. Our results elucidated a metabolic network by which glutamine metabolism regulates the MTORC1-macroautophagy/autophagy pathway through two independent branches involving glutaminolysis and ASNS-GABA shunt. αKG: alpha-ketoglutarate; AMPK: AMP-activated protein kinase; ASNS: asparagine synthetase (glutamine-hydrolyzing); GLUD/GDH: glutamate dehydrogenase; GLS: glutaminase; GOT1: glutamic-oxaloacetic transaminase 1; MTORC1: mechanistic target of rapamycin kinase complex 1; TCA: tricarboxylic acid.
癌细胞主要通过谷氨酰胺分解代谢途径（glutaminolysis）来代谢谷氨酰胺，该代谢途径会激活 MTORC1。AMPK-MTORC1 信号轴是细胞生长和增殖的关键调节剂。我们最近的研究表明，谷氨酰胺和 AMPK 之间的联系不仅限于谷氨酰胺分解代谢。相反，我们证明了 ASNS（天冬酰胺合成酶（谷氨酰胺水解））和 GABA 分流在谷氨酰胺充足时对 AMPK-MTORC1 轴的代谢控制中起着至关重要的作用。我们的研究结果阐明了一个代谢网络，即谷氨酰胺代谢通过两条独立的分支（涉及谷氨酰胺分解代谢和 ASNS-GABA 分流）来调节 MTORC1-巨自噬/自噬途径，从而调节 MTORC1-巨自噬/自噬途径。αKG：α-酮戊二酸；AMPK：AMP 激活的蛋白激酶；ASNS：天冬酰胺合成酶（谷氨酰胺水解）；GLUD/GDH：谷氨酸脱氢酶；GLS：谷氨酰胺酶；GOT1：谷草转氨酶 1；MTORC1：雷帕霉素靶蛋白激酶复合物 1；TCA：三羧酸循环。
