Department of Biotechnology, IIT Kharagpur, Kharagpur 721302, West Bengal, India

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.