Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria.
Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria.
Dev Cell. 2014 Jun 23;29(6):729-39. doi: 10.1016/j.devcel.2014.04.025.
Membrane phospholipids typically contain fatty acids (FAs) of 16 and 18 carbon atoms. This particular chain length is evolutionarily highly conserved and presumably provides maximum stability and dynamic properties to biological membranes in response to nutritional or environmental cues. Here, we show that the relative proportion of C16 versus C18 FAs is regulated by the activity of acetyl-CoA carboxylase (Acc1), the first and rate-limiting enzyme of FA de novo synthesis. Acc1 activity is attenuated by AMPK/Snf1-dependent phosphorylation, which is required to maintain an appropriate acyl-chain length distribution. Moreover, we find that the transcriptional repressor Opi1 preferentially binds to C16 over C18 phosphatidic acid (PA) species: thus, C16-chain containing PA sequesters Opi1 more effectively to the ER, enabling AMPK/Snf1 control of PA acyl-chain length to determine the degree of derepression of Opi1 target genes. These findings reveal an unexpected regulatory link between the major energy-sensing kinase, membrane lipid composition, and transcription.
膜磷脂通常含有 16 和 18 个碳原子的脂肪酸 (FAs)。这种特定的链长在进化上高度保守，据推测，它为生物膜提供了最大的稳定性和动态特性，以响应营养或环境信号。在这里，我们表明 C16 与 C18 FAs 的相对比例受乙酰辅酶 A 羧化酶 (Acc1) 的活性调节，Acc1 是 FA 从头合成的第一个也是限速酶。Acc1 的活性受到 AMPK/Snf1 依赖性磷酸化的减弱，这是维持适当的酰链长度分布所必需的。此外，我们发现转录抑制剂 Opi1 优先结合 C16 而不是 C18 磷脂酸 (PA) ：因此，含有 C16 链的 PA 更有效地将 Opi1 隔离到 ER 中，从而使 AMPK/Snf1 能够控制 PA 酰链长度，从而确定 Opi1 靶基因去阻遏的程度。这些发现揭示了主要的能量感应激酶、膜脂质组成和转录之间的一种意想不到的调节联系。
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