Systems-level Characterization of Mitochondrial Function in Disease and Health
Isha Jain, Harvard University/MIT
Inborn errors of metabolism can result in devastating outcomes for patient health. Genetic lesions affecting mitochondrial integrity and function can lead to muscle weakness, visual and hearing defects, developmental defects, etc. As a consequence, patients suffering from mitochondrial disorders have increased mortality and morbidity. Understanding mitochondrial physiology and function will inform our understanding of human health and disease states.
Mitochondria possess their own genome, which encodes proteins in the electron transport chain. The remainder of proteins needed for proper function are imported from the cytoplasm. Therefore, genetic lesions in nuclear DNA or mitochondrial DNA can result in aberrant function. Such lesions can lead to impaired energy production, metabolic imbalance, etc.
We aim to (1) characterize mitochondrial disease states resulting from genetic lesions and use this information to (2) identify novel therapeutic targets. The emergence of high-throughput technology has allowed for a comprehensive biological characterization of cellular models. We generate genetic models of mitochondrial disease states and use genome-wide approaches to characterize the transcriptome, metabolome, etc. of the disease state. This allows us to identify the primary biological pathways contributing to disease pathology. We then use systems genetics approaches to identify therapeutic targets in the context of such perturbed pathways.
Abstract Author(s): Isha Jain, Vamsi Mootha