Humans are exposed to hundreds of thousands of metabolites through diet and modern life, and cells manage this complexity through precise compartmentalization. Our lab investigates how intracellular organelles regulate metabolite concentrations and shape dynamic cellular environments, with a focus on solute carriers and other transport proteins. One core area of research centers on NAD metabolism. Declining NAD levels are linked to aging and mitochondrial dysfunction. We study how NAD compartmentalization influences cellular function and aging, highlighting our discovery of the mitochondrial NAD transporter SLC25A51 as a regulator of senescence in pancreatic beta cells. Its deletion improves glucose homeostasis and prevents beta cell dysfunction in diabetes models. A second major focus is the identification and characterization of mitochondrial transporters, many of which remain functionally unassigned. We have developed a high-resolution mass spectrometry-based screening strategy to uncover transporter substrates. This approach complements a broader platform integrating functional genomics, metabolomics, imaging, structural biology, and mouse models. Together, our work seeks to answer fundamental questions: How do mitochondria maintain metabolite homeostasis? How is transporter function tuned to metabolic states, environmental conditions, and developmental cues? And how do these processes impact physiology in health and disease?
Nora Kory (Sun,) studied this question.