Sarkar Priyanka, Misra Susmita, Ghosal Agamani, Mukherjee Soumyajit, Ghosh Alok, Sundaram Geetanjali
Department of Biochemistry, University of Calcutta, Kolkata 700019, India.
Biol Open. 2023 Oct 15;12(10). doi: 10.1242/bio.060145. Epub 2023 Oct 24.
Cell cycle regulation in response to biochemical cues is a fundamental event associated with many diseases. The regulation of such responses in complex metabolic environments is poorly understood. This study reveals unknown aspects of the metabolic regulation of cell division in Schizosaccharomyces pombe. We show that changing the carbon source from glucose to lactic acid alters the functions of the cyclin-dependent kinase (CDK) Cdc2 and mitogen-activated protein kinase (MAPK) Sty1, leading to unanticipated outcomes in the behavior and fate of such cells. Functional communication of Cdc2 with Sty1 is known to be an integral part of the cellular response to aberrant Cdc2 activity in S. pombe. Our results show that cross-talk between Cdc2 and Sty1, and the consequent Sty1-dependent regulation of Cdc2 activity, appears to be compromised and the relationship between Cdc2 activity and mitotic timing is also reversed in the presence of lactate. We also show that the biochemical status of cells under these conditions is an important determinant of the altered molecular functions mentioned above as well as the altered behavior of these cells.
细胞周期对生化信号的响应调节是与多种疾病相关的基本事件。在复杂代谢环境中这种响应的调节尚不清楚。本研究揭示了粟酒裂殖酵母细胞分裂代谢调节中未知的方面。我们表明，将碳源从葡萄糖改为乳酸会改变细胞周期蛋白依赖性激酶（CDK）Cdc2和丝裂原活化蛋白激酶（MAPK）Sty1的功能，导致这些细胞的行为和命运出现意外结果。已知Cdc2与Sty1的功能通讯是粟酒裂殖酵母细胞对异常Cdc2活性作出反应的一个组成部分。我们的结果表明，Cdc2与Sty1之间的相互作用以及随之而来的Sty1对Cdc2活性的依赖性调节似乎受到损害，并且在乳酸存在的情况下，Cdc2活性与有丝分裂时间之间的关系也发生了逆转。我们还表明，在这些条件下细胞的生化状态是上述分子功能改变以及这些细胞行为改变的重要决定因素。
