Adaptation to nutrient scarcity involves an orchestrated response of metabolic and signaling pathways to maintain homeostasis. We provide evidence that lysosomal export of cystine coordinates remobilization of internal nutrient stores with reactivation of the growth regulator TORC1 signaling upon fasting in the Drosophila fat body. Mechanistically, cystine is reduced to cysteine and metabolized to acetyl-CoA by consuming lipids. In turn, acetyl-CoA retains carbons from alternative amino acids in the form of TCA cycle intermediates, thereby restricting amino acids availability, notably aspartate. This process limits TORC1 reactivation to maintain autophagy and allows animals to cope with starvation periods. We propose that cysteine metabolism mediates a communication between lysosomes and mitochondria to maintain the balance between nutrient supply and consumption under starvation, highlighting how changes in diet divert the fate of an amino acid into a growth suppressive program.

中文翻译：

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溶酶体胱氨酸流出通过TCA循环反对mTORC1的再激活。

对营养物缺乏的适应涉及新陈代谢和信号通路的协调响应，以维持体内平衡。我们提供的证据表明，在果蝇脂肪体内禁食后，胱氨酸的溶酶体输出可协调内部营养物储存的迁移，并通过生长调节剂TORC1信号的活化而重新激活。从机理上讲，通过消耗脂质，胱氨酸还原为半胱氨酸并代谢为乙酰辅酶A。反过来，乙酰辅酶A以TCA循环中间体的形式保留了其他氨基酸的碳，从而限制了氨基酸的利用率，尤其是天冬氨酸。该过程限制了TORC1的重新激活以维持自噬，并允许动物应对饥饿期。