生物谷报道：日本科学家近日研究发现，当细胞中能量减少时，一种名为eNoSC的蛋白质联合体能够减慢蛋白质的生产。这对于细胞存活具有关键作用，缺乏这一联合体组分的缺能细胞会快速自我破坏。相关论文发表在《细胞》（Cell）杂志上。
蛋白质由核糖体建造，之前的研究表明，核糖体RNA（rRNA）基因的表达部分是由组蛋白的化学变化调节的。
在最新的研究中，日本筑波大学的Junn Yanagisawa和同事鉴别出了eNoSC，正是它造成了这些化学变化。
eNoSC包含三种蛋白，其中之一为SIRT1。研究人员认为，SIRT1在细胞应付能量减少过程中发挥了作用。eNoSC减少了葡萄糖缺乏细胞中rRNA的生产，为能量缺乏时减慢蛋白质生产提供了新方式。
更进一步，研究人员发现，当eNoSC三种蛋白中任意一种的生产被抑制时，葡萄糖缺乏的细胞会更快地死亡。
美国麻省大学医学院的Janet Stein认为，这一发现“帮助我们更深入地理解能量限制怎样调节核糖体基因表达。”不过他同时表示，此次研究是在癌细胞中进行的，而癌细胞本身就具有特别高的能量需求，接下来的工作应该是在非癌细胞中重复这一实验。
Yanigasawa说，他和同事目前正在比较非癌细胞和癌细胞对能量减少的反应。他说：“此类研究将为新型的癌症治疗策略提供基础。”（科学网 梅进/编译）
生物谷推荐原始出处：
Cell, Vol 133, 627-639, 16 May 2008
Article
Epigenetic Control of rDNA Loci in Response to Intracellular Energy Status
Akiko Murayama,1,2,5,6 Kazuji Ohmori,1,6 Akiko Fujimura,1 Hiroshi Minami,4 Kayoko Yasuzawa-Tanaka,1 Takao Kuroda,1 Shohei Oie,1 Hiroaki Daitoku,2 Mitsuru Okuwaki,3 Kyosuke Nagata,3 Akiyoshi Fukamizu,2 Keiji Kimura,1 Toshiyuki Shimizu,4 and Junn Yanagisawa1,
1 Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
2 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
3 Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
4 International Graduate School of Arts and Sciences, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan
5 PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama, Japan
Corresponding author
Junn Yanagisawa
junny@agbi.tsukuba.ac.jp
Intracellular energy balance is important for cell survival. In eukaryotic cells, the most energy-consuming process is ribosome biosynthesis, which adapts to changes in intracellular energy status. However, the mechanism that links energy status and ribosome biosynthesis is largely unknown. Here, we describe eNoSC, a protein complex that senses energy status and controls rRNA transcription. eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. Both SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression, suggesting that a change in the NAD+/NADH ratio induced by reduction of energy status could activate SIRT1, leading to deacetylation of histone H3 and dimethylation at Lys9 by SUV39H1, thus establishing silent chromatin in the rDNA locus. Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. These findings provide key insight into the mechanisms of energy homeostasis in cells.
