Ken Nakamura’s lab studies mitochondria, the “power centers” inside each cell that convert nutrients into ATP, a form of energy the cell can use. The lab has two broad, intertwined objectives. The first is to understand how mitochondria and energy metabolism normally support the function of healthy brain neurons. The second is to understand how disruptions in mitochondrial function and metabolism contribute to neurodegenerative diseases, especially Parkinson’s disease, Alzheimer’s disease, and mitochondrial disorders, and to use these insights to develop new therapeutic approaches that boost energy levels in vulnerable cells.
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Neurons have long been known to rely heavily on mitochondrial energy production, but scientists have lacked the tools to understand the mechanisms of this dependence. Nakamura’s lab has developed tools to monitor ATP production and study metabolism in normal and diseased neurons, and used them to show that energy failure can result from an imbalance between excessive energy consumption due to increased neural activity and insufficient production. They have also developed cutting-edge approaches to track the fates of individual mitochondria in neurons over time, and used them to make important discoveries about the mitochondrial life cycle in neurons and how it is disrupted in Parkinson’s disease.
Nakamura’s group also provided the first comprehensive map of mitochondrial genes and pathways that maintain cellular energy levels. ATP is the central energy carrier, but the pathways that regulate ATP levels are not systematically understood. The team’s studies provide insight into which diseases may act through energy failure and identify new therapeutic strategies to correct energy failure in these diseases.