Laboratorio de Biotecnología Microbiana, Instituto Tecnológico Superior de Ciudad Hidalgo, Ciudad Hidalgo, Michoacán, Mexico.
Ingeniería Bioquímica, Laboratorio de Bioquímica del Instituto Tecnológico de Morelia, Av. Tecnológico de Morelia, Morelia, Michoacán, Mexico.
Yeast. 2019 Aug;36(8):487-494. doi: 10.1002/yea.3399. Epub 2019 Jul 24.
The switch between mitochondrial respiration and fermentation as the main ATP production pathway through an increase glycolytic flux is known as the Crabtree effect. The elucidation of the molecular mechanism of the Crabtree effect may have important applications in ethanol production and lay the groundwork for the Warburg effect, which is essential in the molecular etiology of cancer. A key piece in this mechanism could be Snf1p, which is a protein that participates in the nutritional response including glucose metabolism. Thus, this work aimed to recognize the role of the SNF1 gene on the glycolytic flux and mitochondrial respiration through the glucose concentration variation to gain insights about its relationship with the Crabtree effect. Herein, we found that SNF1 deletion in Saccharomyces cerevisiae cells grown at 1% glucose, decreased glycolytic flux, increased NAD(P)H concentration, enhanced HXK2 gene transcription, and decreased mitochondrial respiration. Meanwhile, the same deletion increased the mitochondrial respiration of cells grown at 10% glucose. Altogether, these findings indicate that SNF1 is important to respond to glucose concentration variation and is involved in the switch between mitochondrial respiration and fermentation.
线粒体呼吸和发酵之间作为主要的 ATP 产生途径的转换,通过增加糖酵解通量,被称为克氏效应(Crabtree effect)。阐明克氏效应的分子机制可能在乙醇生产中有重要应用,并为沃伯格效应(Warburg effect)奠定基础,沃伯格效应是癌症分子病因学中的关键因素。该机制中的一个关键部分可能是 Snf1p,它是一种参与营养响应包括葡萄糖代谢的蛋白质。因此,这项工作旨在通过葡萄糖浓度的变化来识别 SNF1 基因对糖酵解通量和线粒体呼吸的作用,以深入了解其与克氏效应的关系。在此,我们发现,在 1%葡萄糖生长的酿酒酵母细胞中删除 SNF1 基因,会降低糖酵解通量,增加 NAD(P)H 浓度,增强 HXK2 基因转录,并降低线粒体呼吸。同时,相同的缺失会增加在 10%葡萄糖生长的细胞的线粒体呼吸。总之,这些发现表明,SNF1 对于响应葡萄糖浓度变化很重要,并参与了线粒体呼吸和发酵之间的转换。