About this Research Topic
Mitochondrial diseases represent a significant medical and scientific challenge. There are currently no effective interventions for patients suffering from genetic mitochondrial disorders; treatment being generally limited to palliative care. Genetic mitochondrial diseases arise from defects in nuclear or mitochondrial genes, have a high degree of phenotypic heterogeneity, and are generally clinically defined syndromes characterized by shared pathological features.
Aside from palliative care, efforts at intervening in mitochondrial disorders have included antioxidant therapy, dietary modulation, vitamin supplementation, and treatment with dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase. Unfortunately, while modest benefits have been observed in isolated human trials or animal studies, none of these approaches have led to substantial advances in the treatment of human mitochondrial diseases.
Recent studies, which targeted intracellular signaling through the mechanistic target of rapamycin (mTOR) and hypoxia inducible response pathways, have reported dramatic attenuation of phenotypic markers of disease in yeast, cell culture, and mouse models. Most notable are recent reports that mTOR inhibition by rapamycin and hypoxia (acting, presumably, through activation of Hif-1) substantially increase survival and attenuate neurodegenerative phenotypes in the premier mouse model of human mitochondrial disease, the Leigh syndrome model Ndufs4 -/- mouse. These studies provide the strongest evidence to date that intervention in mitochondrial disorders is possible, while also indicating that it is time for a paradigm shift in our approach to understanding and intervening in mitochondrial disease.
This aim of this Research Topic is to explore the role of intra- and extra-cellular signaling in the etiology, pathogenesis, and treatment of diseases resulting from mitochondrial dysfunction. We welcome the submission of any Original Research articles, Perspectives, Reviews, and Case Reports related to the role of signaling in disorders arising from mitochondrial dysfunction. We particularly welcome manuscripts focusing on severe mitochondrial diseases arising from defects in single genes, such as Leigh and MELAS syndromes. We also welcome submissions critical of the central theme of this topic, i.e. articles supportive of bioenergetics as a target in diseases of altered mitochondrial function.
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