Biomarkers for mitochondrial energy metabolism diseases

Biomarkers are an indicator of biologic or pathogenic processes, whose function is indicating the presence/absence of disease or monitoring disease course and its response to treatment. Since mitochondrial disorders (MDs) can represent a diagnostic challenge for clinicians, due to their clinical and genetic heterogeneity, the identification of easily measurable biomarkers becomes a high priority. Given the complexity of MD, in particular the primary mitochondrial respiratory chain (MRC) diseases due to oxidative phosphorylation (OXPHOS) dysfunction, a reliable single biomarker, relevant for the whole disease group, could be extremely difficult to find, most of times leading the physicians to better consider a ‘biosignature’ for the diagnosis, rather than a single biochemical marker. Serum biomarkers like lactate and pyruvate are largely determined in the diagnostic algorithm of MD, but they are not specific to this group of disorders. The concomitant determination of creatine (Cr), plasma amino acids, and urine organic acids might be helpful to reinforce the biosignature in some cases. In recent studies, serum fibroblast growth factor 21 (sFGF21) and serum growth differentiation factor 15 (sGDF15) appear to be promising molecules in identifying MD. Moreover, new different approaches have been developed to discover new MD biomarkers. This work discusses the most important biomarkers currently used in the diagnosis of MRC diseases, and some approaches under evaluation, discussing both their utility and weaknesses.