Organelle Crosstalk in Disease and Health

Isha Jain, Harvard University/MIT

Mitochondrial dysfunction results in devastating consequences for patients affected by rare forms of mitochondrial disease as well as more common conditions including Alzheimer’s, Parkinson’s, diabetes and aging. The field of mitochondrial biology has benefited greatly from an in-depth characterization of mitochondrial proteins and biochemical functions.

However, the translation from mitochondrial biology to mitochondrial medicine lags behind, without reliable diagnostic markers or available treatments. With more than 150 genetic lesions affecting one in 5,000 live births, mitochondrial disorders are the most prevalent of the inborn errors of metabolism and among the most debilitating.

Intracellular compartmentalization allows cells to simultaneously perform diverse functions. During states of health, organelle crosstalk allows for a coordinated metabolic response. My research interests lie at the intersection of organelle crosstalk and inborn errors of metabolism. More specifically, I have been studying the pathology and therapeutic targets associated with mitochondrial disease.

I have used genome editing technology to model both primary and secondary mitochondrial disease. I have then performed extensive high-throughput characterization of the disease models. I have used metabolic profiling to characterize the disease state and to discover novel biomarkers for diagnostic tests. Additionally, I have studied how protein mistargeting between organelles can contribute to disease pathology. Such characterization of disease states will allow me to develop biomarkers as well as therapeutics.

Abstract Author(s): Isha Jain, Vamsi Mootha