Just like a comic book super hero, you could say that the enzyme superoxide dismutase (SOD1) has a secret identity. Since its discovery in 1969, scientists believed SOD1's only role was to protect living cells against damage from free radicals. Now, researchers at the Johns Hopkins Bloomberg School of Public Health have discovered that SOD1 protects cells by regulating cell energy and metabolism. The results of their research were published January 17, 2013, in the journal Cell.

Transforming oxygen to energy for growth is key to life for all living cells, which happens either through respiration or fermentation. When oxygen is plentiful, respiration normally takes over; however certain cells fail to respire in spite of abundant oxygen and instead ferment, leading to uncontrolled cell growth-a hallmark of cancer.

Using the baker's yeast S. cerevisiae as well as a human cell line, researchers Valeria C. Culotta, PhD, and colleague Amit Reddi from the Department of Biochemistry and Molecular Biology determined that SOD1 transmits signals from oxygen and glucose to repress respiration. This signaling is accomplished through SOD1 protection of another enzyme known as casein kinase 1-gamma (CK1γ), which is an important key to the switch between respiration and fermentation.

"SOD enzymes are present in virtually all living cells, from the most ancient bacteria to every cell in the human body," explained Culotta. "I've been telling my students to think of SOD1 as a superhero. It not only defends cells from damaging free radicals, but also has a secret life as a guardian of cell energy and metabolism."

"Our findings provide new clues as to how rapidly dividing cells-from yeast to human cancers-may escape the urge to respire and instead choose fermentation to promote rapid growth," said Culotta.

"SOD1 has long been recognized as an important enzyme in protection from oxidative stress, but this work establishes an important new function for the enzyme in cellular metabolism," said Vernon Anderson, PhD, of the National Institutes of Health's National Institute of General Medical Sciences, which partly funded the study. "The results provide important insight into how SOD1 and oxygen radicals push cellular energy metabolism towards fermentation, a feature of some disease states, including cancer."

"SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration" was written by Amit R. Reddi and Valeria C. Culotta.

The research was supported by the JHU National Institute for Environmental Health Sciences Center and from the National Institutes of Health grants GM050016 and GM093550.