Rego António, Duarte Ana M, Azevedo Flávio, Sousa Maria J, Côrte-Real Manuela, Chaves Susana R
Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, Braga, Portugal.
Microb Cell. 2014 Aug 27;1(9):303-314. doi: 10.15698/mic2014.09.164.
Acetic acid triggers apoptotic cell death in , similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria.
乙酸在 中引发凋亡性细胞死亡，类似于哺乳动物的细胞凋亡。为了揭示这一过程的新调节因子，我们分析了MAPK信号传导受损是否会影响乙酸诱导的细胞凋亡，发现交配信息素反应，尤其是细胞壁完整性途径是主要的介导因素，特别是后者，我们对其进行了进一步的表征。筛选该途径的下游效应物，即转录因子Rlm1p的靶标，突出了细胞壁重塑减少对乙酸抗性尤为重要。因此，调节细胞表面动力学成为提高乙酸抗性的有力策略，在使用酵母的工业发酵以及生物医学中具有潜在应用，可利用结肠癌细胞对肠道丙酸杆菌产生的乙酸诱导的细胞凋亡更高的敏感性。
