Variety is the spice of life: how to explore a redox-dependent heterogeneity in genomically identical cellular populations

Cellular heterogeneity is a widespread phenomenon, existing across organisms and serving a crucial role in evolution and cell survival. Genetically identical cells may as a result present in a variety of forms with different gene and protein expressions, as well as oxidation level. As a result, a wide range of methodologies and techniques for dissecting different types of genetic, proteomic, and phenotypic heterogeneous traits have emerged in recent years in an effort to better understand how diversity exists within a single population and its effects therein. A key area of interest seeks to establish the ways in which cellular heterogeneity and aging processes interact with each other. Here, we discuss recent developments in defining cellular heterogeneity, specifically focusing on redox-dependent heterogeneity, its characterization, quantification, and behavior. We further expand on potential applications of a cell sorting-based methodology for distinguishing between cells harboring different redox statuses. As an example, we use organelle-specific fluorescence protein-based probes to examine the crosstalk between cytosol and mitochondria in a yeast strain lacking glutathione reductase. Together, these may have wide-reaching implications for future research into redox-associated factors, as well as mechanisms of redox-dependent heterogeneity and its influence on organelles and the cell at large.