NIH Reporter #4DP2GM146255-02

Off the beaten path(way): Spatiotemporal investigation of protein assemblies controlling mitochondrial metabolism

The award funds research to study protein assemblies controlling mitochondrial metabolism, focusing on the heme metabolon. It integrates structural biology and proteomics to understand metabolic processes and their implications for diseases.

Description

This project aims to determine how communities of proteins assemble and disassemble to control cellular metabolism, uncovering fundamental principles underlying the formation of cellular machines necessary for life. The investigation focuses on the heme metabolon, a dynamic cluster of proteins, cofactors, and small molecules that control a metabolic process, across multiple biological systems. The project involves isolating and solving the structure of the heme metabolon, determining the dynamics of metabolon formation, and investigating how defects in assembly steps alter metabolic output using techniques such as high-resolution cryo-EM, time-resolved proteomics, and metabolomics. The goal is to transform the static view of metabolism into a 3D movie of a living metabolic machine, with broad implications for understanding cancer progression, diabetes, and immune responses.

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