Rebsamen Manuele, Superti-Furga Giulio
a CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , Vienna , Austria.
b Center for Physiology and Pharmacology, Medical University of Vienna , Vienna , Austria.
Autophagy. 2016 Jun 2;12(6):1061-2. doi: 10.1080/15548627.2015.1091143. Epub 2015 Oct 2.
The mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) acts as a crucial regulator of cellular metabolism by integrating growth factor presence, energy and nutrient availability to coordinate anabolic and catabolic processes, and controls cell growth and proliferation. Amino acids are critical for MTORC1 activation, but the molecular mechanisms involved in sensing their presence are just beginning to be understood. We recently reported that the previously uncharacterized amino acid transporter SLC38A9 is a member of the lysosomal sensing machinery that signals amino acid availability to MTORC1. SLC38A9 is the first component of this complex shown to physically engage amino acids, suggesting a role at the core of the amino acid-sensing mechanism.
雷帕霉素机制性靶点(丝氨酸/苏氨酸激酶)复合物1(MTORC1)通过整合生长因子的存在、能量和营养物质的可利用性来协调合成代谢和分解代谢过程,从而作为细胞代谢的关键调节因子,并控制细胞生长和增殖。氨基酸对MTORC1的激活至关重要,但其感知氨基酸存在的分子机制才刚刚开始被了解。我们最近报道,以前未被鉴定的氨基酸转运蛋白SLC38A9是溶酶体感知机制的成员,该机制将氨基酸的可利用性信号传递给MTORC1。SLC38A9是该复合物中首个被证明能与氨基酸直接结合的成分,这表明它在氨基酸感知机制的核心发挥作用。