Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids

Wen Fang, Liu Jiang, Yibing Zhu, Sen Yang, Hong Qiu, Jiou Cheng, Qingxi Liang, Zong-cai Tu and Cunqi Ye ()
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Wen Fang: Zhejiang University
Liu Jiang: Zhejiang University
Yibing Zhu: Zhejiang University
Sen Yang: Zhejiang University
Hong Qiu: Zhejiang University
Jiou Cheng: Zhejiang University
Qingxi Liang: Zhejiang University
Zong-cai Tu: Jiangxi Normal University
Cunqi Ye: Zhejiang University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-38289-9

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