INSIDE OUR CELLS, TINY FACTORIES convert nutrients from food into a form of energy that cells can use. Failure of these factories, known as mitochondria, can lead to metabolic disorders that are difficult to diagnose and even harder to treat.
Now researchers have identified an important regulator of cellular energy production that could aid in the diagnosis and treatment of a range of conditions. In a study published on Dec. 18, 2014, in the journal Cell, the researchers demonstrated that an enzyme known as Sirtuin 4 acts as a guardian of cellular energy production.
“The finding has broad implications in human health,” said Ileana Cristea, associate professor of molecular biology, who led the study. “Stress, nutritional deficiencies and viral infections can impact Sirtuin 4 functions and trigger dysfunction in energy metabolism,” Cristea said. “With this knowledge, we now have a new regulatory point that can be targeted in therapeutic interventions.”
Cristea’s team discovered that Sirtuin 4 turns off energy production by removing certain protein modifications, called lipoylation, from a key part of the energy-making machinery, called the pyruvate dehydrogenase complex.
The research team included former Postdoctoral Researcher Rommel Mathias and Associate Research Scholar Todd Greco in the Cristea laboratory, as well as collaborators Thomas Shenk, the James A. Elkins Jr. Professor in the Life Sciences, and Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology.
Cristea’s research is supported by the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Disease, the National Institute of General Medical Sciences, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
–By Catherine Zandonella