Oxidative stress in inherited mitochondrial diseases

• Published in: Free radical biology & medicine Vol. 88; no. Pt A; pp. 10 - 17
• Main Authors: Hayashi, Genki, Cortopassi, Gino
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: Free radicals; Friedreich ataxia; Humans; Inflammation; Leber hereditary optic neuropathy; Leigh syndrome; MELAS; MERRF; Mitochondrial disease; Mitochondrial Diseases - physiopathology; Neurodegeneration; Neuroinflammation; Oxidative Stress; Reactive Oxygen Species; Oxidative stress; Leigh syndrome; MERRF; Free radicals; Neurodegeneration; Leber hereditary optic neuropathy; Neuroinflammation; Friedreich ataxia; Inflammation; MELAS; Mitochondrial disease
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2015.05.039

Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for “oxidative stress” citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia. •Mitochondrial diseases are rare, orphan diseases with no known, proven, curative therapy.•The involvement of oxidative stress in the pathomechanisms of five mitochondrial diseases is reviewed.•The strongest support for an oxidative pathomechanism was observed in Friedreich ataxia.•Support for an oxidative pathomechanism was also identified in MELAS, MERRF, LS, and LHON.