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Role of Mitochondria in Generation of Phenotypic Heterogeneity in Yeast
Journal of the Indian Institute of Science ( IF 2.3 ) Pub Date : 2020-05-30 , DOI: 10.1007/s41745-020-00176-3
Riddhiman Dhar

A cell’s phenotype is determined by its genome sequence and epigenetic state which translate into the biochemical reactions occurring inside the cells. As these biochemical processes are driven by small biological molecules, stochastic fluctuations may arise in the number of these biological molecules inside the cell and in the interactions between these molecules. These fluctuations can cause temporal variations in the cellular processes leading to variations in phenotype between two cells present in a population under identical environmental condition. Phenotypic variations in a population can enable a small fraction of cells to survive sudden changes in the environmental condition, as some of the cells are always prepared for such a change. Phenotypic variations can thus have very important implications for survival of a cell population and have been shown to affect our ability to treat human diseases—from eradication of a bacterial infection to treatment of cancer. In this review, I discuss the role of mitochondria, an important organelle in all eukaryotic cells, in generation of phenotypic heterogeneity. Mitochondria contains its own genome in multiple copies per cell and many proteins and RNA molecules required for proper functioning of mitochondria are present on the mitochondrial genome. Variations in number of copies of the mitochondrial genomes can thus lead to variations in mitochondrial functional state. As mitochondria have important roles in several cellular process, this can lead to variations in several cellular phenotypes including drug resistance. In this context, I also discuss the role of mitochondria in human diseases where mitochondrial heterogeneity could have important implications for disease progression and therapy. Thus, understanding the role of mitochondria in generation of phenotypic variation assumes significant importance in the context of human diseases as well as emergence of drug resistance.

中文翻译:

线粒体在酵母表型异质性产生中的作用

细胞的表型由其基因组序列和表观遗传状态决定,这些状态转化为细胞内发生的生化反应。由于这些生化过程是由小生物分子驱动的,因此细胞内这些生物分子的数量以及这些分子之间的相互作用可能会出现随机波动。这些波动会导致细胞过程的时间变化,从而导致在相同环境条件下群体中存在的两个细胞之间的表型发生变化。群体中的表型变异可以使一小部分细胞能够在环境条件的突然变化中存活下来,因为一些细胞总是为这种变化做好准备。因此,表型变异对细胞群的存活具有非常重要的影响,并且已被证明会影响我们治疗人类疾病的能力——从根除细菌感染到治疗癌症。在这篇综述中,我讨论了线粒体(所有真核细胞中的重要细胞器)在产生表型异质性中的作用。线粒体在每个细胞中包含多个拷贝的自身基因组,并且线粒体基因组上存在线粒体正常功能所需的许多蛋白质和 RNA 分子。因此,线粒体基因组拷贝数的变化会导致线粒体功能状态的变化。由于线粒体在多种细胞过程中具有重要作用,这会导致多种细胞表型的变化,包括耐药性。在这种情况下,我还讨论了线粒体在人类疾病中的作用,其中线粒体异质性可能对疾病进展和治疗产生重要影响。因此,了解线粒体在表型变异产生中的作用在人类疾病以及耐药性出现的背景下具有重要意义。
更新日期:2020-05-30
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