Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang, 330022, China.
Nat Commun. 2023 May 2;14(1):2504. doi: 10.1038/s41467-023-38289-9.
Methionine restriction (MR) provides metabolic benefits in many organisms. However, mechanisms underlying the MR-induced effect remain incompletely understood. Here, we show in the budding yeast S. cerevisiae that MR relays a signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic mitochondria to nitrogenic anabolism. In particular, decreases in cellular SAM constrain lipoate metabolism and protein lipoylation required for the operation of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete glucose oxidation with an exit of acetyl-CoA and α-ketoglutarate from the TCA cycle to the syntheses of amino acids, such as arginine and leucine. This mitochondrial response achieves a trade-off between energy metabolism and nitrogenic anabolism, which serves as an effector mechanism promoting cell survival under MR.
甲硫氨酸限制（MR）为许多生物体提供代谢益处。然而，MR 诱导效应的机制仍不完全清楚。在这里，我们在芽殖酵母 S. cerevisiae 中表明，MR 将 S-腺苷甲硫氨酸（SAM）剥夺的信号传递给适应氮同化的生物能线粒体。具体来说，细胞内 SAM 的减少限制了脂酰辅酶 A 的代谢和蛋白质的脂酰化，这是线粒体三羧酸（TCA）循环运作所必需的，导致不完全的葡萄糖氧化，乙酰辅酶 A 和 α-酮戊二酸从 TCA 循环中逸出，用于合成氨基酸，如精氨酸和亮氨酸。这种线粒体反应在能量代谢和氮同化之间实现了权衡，这是一种效应机制，有助于细胞在 MR 下存活。
