Diagnostic approach to mitochondrial disorders: the need for a reliable biomarker

Mitochondrial diseases (MD) are disorders caused by impairment of the mitochondrial electron transport chain (ETC). Phenotypes are polymorphous and may range from pure myopathy to multisystemic disorders. The genetic defect can be located on mitochondrial or nuclear DNA. The ETC is needed for oxidative phosphorylation (which provides the cell with the most efficient energetic outcome in terms of ATP production), and consists of five multimeric protein complexes located in the inner mitochondrial membrane. The ETC also requires cytochrome c and a small electron carrier, coenzyme Q10. One of the pathogenic mechanisms of ETC disorders is excessive accumulation of reactive oxygen species (ROS). Mitochondrial dysfunction and oxidative stress appear to have a strong impact also on the pathogenesis of neurodegenerative diseases. At present, diagnosis of MD requires a complex approach: measurement of serum lactate, exercise testing, electromyography, magnetic resonance spectroscopy, muscle histology and enzymology, and genetic analysis. Biomarkers are molecules associated with biological processes or regulatory mechanisms. A reliable biomarker for the screening or diagnosis of MD is still needed. In this paper we review the diagnostic approach to MD, from serum lactate to other blood and urinary markers, from muscular biopsy to imaging studies, and we highlight some potentially interesting perspectives in this field.