Invention A test for mitochondrial health
Inventor Ileana Cristea, professor of molecular biology
What it does The role of mitochondria — which are known as the power plants of the cell — in human health is an active area of research. A team led by Ileana Cristea is pioneering methods to monitor and explore molecular regulators that have implications for the research and treatment of mitochondrial diseases as well as cancer, aging and viral infections.
Cristea’s research group has identified new enzymatic activity by an important regulator of cellular energy production known as sirtuin 4. The researchers demonstrated that sirtuin 4 acts in mitochondria to turn off energy production by inhibiting an important piece of the energy-making machinery, the pyruvate dehydrogenase complex. Sirtuin 4 inhibits pyruvate dehydrogenase activity through a process known as delipoylation.
The team created an assay to accurately measure delipoylation in cells or tissues, which can be used to monitor the activities of sirtuin 4 and the pyruvate dehydrogenase complex. This assay can be performed in any type of cell, tissue or patient sample. The test can help researchers quickly assess the activity of sirtuin 4 and discover ways to inhibit it to boost mitochondrial health, or, alternatively, activate the enzyme to shut off harmful mitochondrial activity.
Cristea noted that stress, nutritional deficiencies and viral infections can destabilize sirtuin 4 functions and trigger dysfunction in energy metabolism. An assay to detect sirtuin 4 could help researchers design therapeutic interventions that restore mitochondrial health. Pyruvate dehydrogenase complex deficiencies have been linked to severe mitochondrial diseases that lead to intellectual disability, loss of balance and brain malformation. Given the finding of the Cristea lab that sirtuin 4 regulates the activity of the pyruvate dehydrogenase complex, these assays can provide a means for understanding the causes of these diseases. Because mitochondria are found in every cell and are fundamental to growth, the test also may aid in studies of cancer, aging, cell signaling and viral infection.
Collaborators Rommel Mathias, a former postdoctoral research fellow in molecular biology; Todd Greco, associate research scholar in molecular biology; Thomas Shenk, the James A. Elkins Jr. Professor in the Life Sciences; and Adam Oberstein, a postdoctoral research fellow in molecular biology.
Development status Patent protection is pending. Princeton is seeking outside interest for further development of this technology.
Funding source National Institutes of Health
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