Glutathione as a Redox Biomarker in Mitochondrial Disease—Implications for Therapy

Gregory M. Enns and Tina M. Cowan; Journal of Clinical Medicine 2017, 6(5), 50; doi:10.3390/jcm6050050

“Do you feel any better?” is a commonly asked question by a physician caring for a patient who has an underlying mitochondrial disorder during a clinic visit, typically after an interval of time following the start of various co-factors, vitamins, or supplements that may have a beneficial effect on mitochondrial function. The lack of validated, widely available, and objective markers of mitochondrial function makes this state-of-the-art of mitochondrial medicine in the 21st century somewhat discouraging.

Dysfunction of the mitochondrial electron transport chain is associated with redox imbalance and abnormally low GSH levels in primary genetic mitochondrial disorders, as well as conditions associated with secondary mitochondrial impairment, such as organic acidemias, Friedreich ataxia, Alzheimer disease, Parkinson disease, amyotropic lateral sclerosis, and Rett syndrome.
Friedreich ataxia patients also have evidence of redox abnormalities and mitochondrial dysfunction. A study of 14 unrelated Friedreich ataxia patients measured total and free GSH concentrations in erythrocytes by HPLC. Patients had a significant reduction of free glutathione levels, although total glutathione levels were comparable to controls. Friedreich ataxia patients were also found to have a significant increase in glutathione bound to hemoglobin in erythrocytes. Glutathione homeostasis was, therefore, considered to be impaired in Friedreich ataxia, raising the possibility that free radicals play a role in disease pathophysiology.