National Institute of General Medical Sciences 2R35GM142553-06

Probing structural and biophysical mechanisms of mitochondrial membrane ultrastructure

This NIH-funded project at Massachusetts General Hospital studies mitochondrial membrane shape and remodeling mechanisms to understand their role in health and disease, using advanced structural biology techniques.

Description

The Chao Lab investigates the molecular mechanisms that determine mitochondrial membrane shape. The principles regulating mitochondrial morphology underlie the organelle’s remarkable range of functional programs (cell death, calcium signaling), and ability to respond to physiological extremes (metabolic stress, oxygen deprivation). Dysfunction in mitochondrial morphology is prevalent in diseases such as neurodegeneration, cancer, and aging. Despite conserved protein components, tissue and organism-specific shapes have evolved to confer functional fidelity and plasticity. The lab aims to understand specialization and diversification in mitochondrial morphology by studying membrane reorganization processes at the micron and nanometer scales, including fusion, fission, and cristae regulation. They utilize in vitro reconstitution and in situ structural visualization, including cryo-ET, to elucidate mechanisms of organelle remodeling. The research will impact mitochondrial biology, structural cell biology, and human health, especially related to diseases associated with mitochondrial dysfunction.

View original record