Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.
PLoS One. 2009 Nov 24;4(11):e8018. doi: 10.1371/journal.pone.0008018.
Sulfur metabolism is required for initiation of cell division, but whether or not it can actively promote cell division remains unknown.
METHODOLOGY/PRINCIPAL FINDINGS: Here we show that yeast cells with more mtDNA have an expanded reductive phase of their metabolic cycle and an increased sulfur metabolic flux. We also show that in wild type cells manipulations of sulfur metabolic flux phenocopy the enhanced growth rate of cells with more mtDNA. Furthermore, introduction of a hyperactive cystathionine-beta-synthase (CBS) allele in wild type cells accelerates initiation of DNA replication.
CONCLUSIONS/SIGNIFICANCE: Our results reveal a novel connection between a key sulfur metabolic enzyme, CBS, and the cell cycle. Since the analogous hyperactive CBS allele in human CBS suppresses other disease-causing CBS mutations, our findings may be relevant for human pathology. Taken together, our results demonstrate the importance of sulfur metabolism in actively promoting initiation of cell division.
硫代谢是细胞分裂启动所必需的,但它是否能主动促进细胞分裂尚不清楚。
方法/主要发现:在这里,我们表明具有更多 mtDNA 的酵母细胞具有扩展的代谢循环还原相和增加的硫代谢通量。我们还表明,在野生型细胞中,硫代谢通量的操作可以模拟具有更多 mtDNA 的细胞的增强生长速率。此外,在野生型细胞中引入超活半胱氨酸-β-合酶(CBS)等位基因可加速 DNA 复制的起始。
结论/意义:我们的结果揭示了关键的硫代谢酶 CBS 与细胞周期之间的新联系。由于人类 CBS 中的类似超活 CBS 等位基因可抑制其他致病 CBS 突变,因此我们的发现可能与人类病理学有关。总之,我们的研究结果表明硫代谢在主动促进细胞分裂的起始中具有重要作用。