Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy: rapid diagnostic method for studying cellular responses to stress and disease

We report an analysis of four strains of baker's yeast ( ) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type and a strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type and a strain differ by knock-out of the nuclear gene encoding , an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter , a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions with a single peak. In contrast, mutant cells and mitochondria produce leptokurtotic distributions that are asymmetric and highly skewed to the right. These distribution changes could be self-consistently modeled with a single, log-normal distribution undergoing a thousand-fold increase in variance of biomolecular composition. These features reflect a new state of stressed or diseased cells that we call a (RBD) that reflects the vital interdependence of mitochondria and the nucleus.