Potentially diagnostic electron paramagnetic resonance spectra elucidate the underlying mechanism of mitochondrial dysfunction in the deoxyguanosine kinase deficient rat model of a genetic mitochondrial DNA depletion syndrome

Free Radical Biology & Medicine
Brian BennettDavid P Dimmock

Abstract

A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunctio...Continue Reading

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Citations

May 28, 2019·Human Molecular Genetics·Xiaoshan ZhouAnna Karlsson
Mar 9, 2019·International Journal of Molecular Sciences·William E AntholineCharles R Myers
Jun 1, 2018·Journal of Neuropathology and Experimental Neurology·Emily M SiebersMichael W Lawlor
Dec 29, 2020·Journal of Inherited Metabolic Disease·Mark A Vanden AvondMichael W Lawlor
Nov 30, 2016·Pediatric Clinics of North America·David P Dimmock, Michael W Lawlor

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