The Ubiquitin Ligase SCFUcc1 Acts as a Metabolic Switch for the Glyoxylate Cycle
The Ubiquitin Ligase SCFUcc1 Acts as a Metabolic Switch for the Glyoxylate Cycle
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DOI：
10.1016/j.molcel.2015.04.013
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发表时间：
2015-07-02
期刊：
影响因子：
16
通讯作者：
Kamura, Takumi
中科院分区：
文献类型：
--
作者：
Nakatsukasa, Kunio;Nishimura, Takashi;Kamura, Takumi
尽管乙醛酸循环在病原体的毒力、植物的种子萌发和真菌的性发育中起着至关重要的作用，但我们对其调控仍有很多需要了解的地方。在这里，我们发现一种以前未被表征的SCFUcc1泛素连接酶在乙醛酸循环中介导柠檬酸合成酶的蛋白酶体降解，以维持葡萄糖生长细胞的代谢稳态。相反，在c -2化合物生长的细胞中，F盒亚基Ucc1的转录下调，这需要增加糖异生的代谢通量。此外，体外分析表明，通过乙醛酸循环再生的草酰乙酸诱导了柠檬酸合酶的构象变化，抑制了SCFUcc1对其的识别和泛素化，表明存在草酰乙酸依赖的正反馈回路，稳定了柠檬酸合酶。我们提出SCFUcc1介导的柠檬酸合酶调控作为葡萄糖酸循环的代谢开关，以响应碳源的变化，从而确保代谢的多功能性和灵活性。
Despite the crucial role played by the glyoxylate cycle in the virulence of pathogens, seed germination in plants, and sexual development in fungi, we still have much to learn about its regulation. Here, we show that a previously uncharacterized SCFUcc1 ubiquitin ligase mediates proteasomal degradation of citrate synthase in the glyoxylate cycle to maintain metabolic homeostasis in glucose-grown cells. Conversely, transcription of the F box subunit Ucc1 is downregulated in C-2-compound-grown cells, which require increased metabolic flux for gluconeogenesis. Moreover, in vitro analysis demonstrates that oxaloacetate regenerated through the glyoxylate cycle induces a conformational change in citrate synthase and inhibits its recognition and ubiquitination by SCFUcc1, suggesting the existence of an oxaloacetate-dependent positive feedback loop that stabilizes citrate synthase. We propose that SCFUcc1 -mediated regulation of citrate synthase acts as a metabolic switch for the glyoxylate cycle in response to changes in carbon source, thereby ensuring metabolic versatility and flexibility.