Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
Cell. 2013 Jul 18;154(2):403-15. doi: 10.1016/j.cell.2013.06.041.
Autophagy is a process of cellular self-digestion induced by various forms of starvation. Although nitrogen deficit is a common trigger, some yeast cells induce autophagy upon switch from a rich to minimal media without nitrogen starvation. We show that the amino acid methionine is sufficient to inhibit such non-nitrogen-starvation (NNS)-induced autophagy. Methionine boosts synthesis of the methyl donor, S-adenosylmethionine (SAM). SAM inhibits autophagy and promotes growth through the action of the methyltransferase Ppm1p, which modifies the catalytic subunit of PP2A in tune with SAM levels. Methylated PP2A promotes dephosphorylation of Npr2p, a component of a conserved complex that regulates NNS autophagy and other growth-related processes. Thus, methionine and SAM levels represent a critical gauge of amino acid availability that is sensed via the methylation of PP2A to reciprocally regulate cell growth and autophagy.
自噬是一种由各种形式的饥饿诱导的细胞自我消化过程。尽管氮缺乏是常见的触发因素，但一些酵母细胞在从富含氮的培养基切换到不含氮的最低限度培养基时，即使没有氮饥饿也会诱导自噬。我们表明，氨基酸蛋氨酸足以抑制这种非氮饥饿（NNS）诱导的自噬。蛋氨酸促进甲基供体 S-腺苷甲硫氨酸（SAM）的合成。SAM 通过甲基转移酶 Ppm1p 抑制自噬并促进生长，Ppm1p 根据 SAM 水平调节 PP2A 的催化亚基。甲基化的 PP2A 促进 NPR2P 的去磷酸化，NPR2P 是一种保守复合物的组成部分，该复合物调节 NNS 自噬和其他与生长相关的过程。因此，蛋氨酸和 SAM 水平代表了氨基酸可用性的关键指标，通过 PP2A 的甲基化来感知，以相互调节细胞生长和自噬。
