Functional Characterization of Redox Switches in Mitochondrial Metabolism

Objective

Reactive oxygen species (ROS) are increasingly recognized as important regulators of cellular signaling, with hydrogen peroxide acting as a key mediator through reversible protein oxidation (redox switches). Mitochondria are the major source of ROS during oxidative phosphorylation, and disturbances in redox balance are a hallmark of mitochondrial diseases, which contribute to both rare inherited disorders and common conditions such as neurodegeneration and cancer. Despite advances in diagnosis, therapeutic progress remains limited, in part because the molecular mechanisms linking mitochondrial dysfunction, redox signaling, and disease progression are poorly understood. This project, MitoSwitch, addresses this knowledge gap by investigating how redox regulation shapes mitochondrial metabolism. I will generate redox proteomic data using two complementary approaches: (i) a model of mitochondrial disease with disrupted redox balance, and (ii) spatially resolved oxidation patterns reflecting local mitochondrial activity. Selected candidate oxidations will then be functionally assessed to identify novel redox switches controlling mitochondrial metabolism. By bridging cellular and tissue-level perspectives, MitoSwitch will advance our understanding of redox biology, reveal molecular mechanisms underlying mitochondrial disease, and deliver broadly applicable methodologies for studying redox regulation in health and pathology.