研究人员发现，在禁食果蝇的脂肪体中，溶酶体输出的半胱氨酸协调了内部营养储存的再动员和雷帕霉素复合物1（TORC1）的生长调节因子的重新激活。从机制上讲，胱氨酸被还原成半胱氨酸，并通过促进CoA代谢被代谢成乙酰辅酶A（乙酰CoA）。反过来，乙酰CoA以三羧酸循环中间物的形式保留了来自替代氨基酸的碳，并限制了生长所需构成要素的可用性。这一过程限制了TORC1的重新激活来维持自噬，并使动物能够应对饥饿期。研究人员提出，半胱氨酸代谢介导了溶酶体和线粒体之间的沟通，突出了饮食的变化如何将一种氨基酸的命运转移到抑制生长的程序中。
据介绍，对营养匮乏的适应涉及代谢和信号通路的协调反应，从而维持平衡。
附：英文原文
Title: Lysosomal cystine mobilization shapes the response of TORC1 and tissue growth to fasting
Author: Patrick Jouandin, Zvonimir Marelja, Yung-Hsin Shih, Andrey A. Parkhitko, Miriam Dambowsky, John M. Asara, Ivan Nemazanyy, Christian C. Dibble, Matias Simons, Norbert Perrimon
Issue&Volume: 2022-02-18
Abstract: Adaptation to nutrient scarcity involves an orchestrated response of metabolic and signaling pathways to maintain homeostasis. We find that in the fat body of fasting Drosophila, lysosomal export of cystine coordinates remobilization of internal nutrient stores with reactivation of the growth regulator target of rapamycin complex 1 (TORC1). Mechanistically, cystine was reduced to cysteine and metabolized to acetyl-coenzyme A (acetyl-CoA) by promoting CoA metabolism. In turn, acetyl-CoA retained carbons from alternative amino acids in the form of tricarboxylic acid cycle intermediates and restricted the availability of building blocks required for growth. This process limited TORC1 reactivation to maintain autophagy and allowed animals to cope with starvation periods. We propose that cysteine metabolism mediates a communication between lysosomes and mitochondria, highlighting how changes in diet divert the fate of an amino acid into a growth suppressive program.
DOI: abc4203
Source: https://www.science.org/doi/10.1126/science.abc4203