ReviewMetabolomics of mitochondrial disease

•Mitochondrial disease (MD) diagnostics has traditionally relied very little on metabolic data.•Recently metabolomics has contributed to several novel approaches and discoveries on MD•We review the application of metabolomics to MD and provide an extensive overview of the reported metabolic perturbations•We highlight the clear potential of metabolomics in the context of diagnostics and mitochondrial medicine•We conclude that metabolomics is more likely to achieve this potential by searching for biosignatures rather than single biomarkers.

Mitochondrial disease (MD) diagnostics and disease progression investigations have traditionally relied very little on metabolic data, due to a lack of biomarker sensitivity and specificity. The recent drive to find novel, low intervention biomarkers and new therapeutic approaches have revived an interest in what metabolic data can offer, as presented in this timely review. We review how metabolomics has been applied to MD and provide an extensive overview of the reported metabolic perturbations and common mechanistic features that may provide a basis for future research. We conclude by highlighting the substantial potential of metabolomics for future diagnostics and mitochondrial medicine.