Metabolic profiling of mitochondrial disease at rest and with exercise

Abstract

The mitochondrial respiratory chain disorders represent a large collection of individually rare syndromes. Their phenotypic heterogeneity, combined with the large number of causal genetic and environmental factors, makes their diagnosis and management challenging. While characterisation of the mitochondrial proteome, in combination with next generation sequencing is transforming their molecular diagnosis, we still lack facile biomarkers and useful therapies. In this talk, I will present our lab's recent efforts applying metabolomics technology to study the cellular and human biochemical response to mitochondrial dysfunction. The results provide new insights into the metabolic ripples that ensue in response to mitochondrial respiratory chain dysfunction to give rise to diverse pathology observed in these disorders. We are combining this cell-based work with studies of patients with mitochondrial disease at rest and with exercise. Our work has implications for discovering new biomarkers of mitochondrial disease, as well as for nominating new therapeutic strategies for these challenging disorders. The mitochondrial respiratory chain disorders represent a large collection of individually rare syndromes. Their phenotypic heterogeneity, combined with the large number of causal genetic and environmental factors, makes their diagnosis and management challenging. While characterisation of the mitochondrial proteome, in combination with next generation sequencing is transforming their molecular diagnosis, we still lack facile biomarkers and useful therapies. In this talk, I will present our lab's recent efforts applying metabolomics technology to study the cellular and human biochemical response to mitochondrial dysfunction. The results provide new insights into the metabolic ripples that ensue in response to mitochondrial respiratory chain dysfunction to give rise to diverse pathology observed in these disorders. We are combining this cell-based work with studies of patients with mitochondrial disease at rest and with exercise. Our work has implications for discovering new biomarkers of mitochondrial disease, as well as for nominating new therapeutic strategies for these challenging disorders.