Role of Mitochondria in Generation of Phenotypic Heterogeneity in Yeast

Abstract

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.