Cryogenic electron paramagnetic resonance spectroscopy of flash-frozen tissue for characterization of mitochondrial disease

Abstract

Electron paramagnetic resonance spectroscopy (EPR) is an analytical technique that, uniquely, can be used to directly interrogate flash-frozen tissue. Quantitative information on the thermodynamic potential of the mitochondrion to synthesize ATP, and the extent of reactive oxygen species-mediated oxidative stress on the mitochondrion and the cell at large, can be obtained. A compromised ability to synthesize ATP and oxidative stress are two of the characteristic sequelae of mitochondrial disease and therapeutic approaches may differ widely depending on which of these is dominant. EPR, therefore, has a role to play in the characterization, diagnosis, and ongoing evaluation of therapies for mitochondrial disease in human patients and model systems. An introduction to mitochondrial disease is followed by a description of EPR, a summary of the EPR signals that can be expected from tissue samples, sample preparation and analytical methods, and a case study in which EPR and complementary techniques were employed on a rat model to study human mitochondrial disease.

Keywords

Mitochondrial disease / electron paramagnetic resonance / electron paramagnetic resonance spectroscopy / mitochondria

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