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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

Gourley, Paul L.; Hendricks, Judy K.; McDonald, Anthony E.; Copeland, Robert G.; Yaffe, Michael P.; Naviaux, Robert K.

We report an analysis of four strains of baker's yeast Saccharomyces cerevisiae 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 0 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 Cox4, 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 reactive biomolecular divergence RBD that reflects the vital interdependence of mitochondria and the nucleus. © 2007 Society of Photo-Optical Instrumentation Engineers.