Marine bacterium sheds light on control of toxic metals

An ocean-dwelling bacterium has provided researchers at the University of East Anglia with fresh insights into how cells protect themselves from the toxic effects of metal ions such as iron and copper.

Although essential to life, metal ions can also generate reactive oxygen species (ROS) – highly reactive molecules that damage cells as they try to form bonds with other molecules. In humans, reactive oxygen species are linked to ageing and also to diseases such as cancers.

To reduce the toxic effects of iron a family of proteins called ferritins store and detoxify the metal ions, keeping the iron in a safe, but accessible form inside cells.

Working with researchers at the University of Essex and the Scripps Institute in California, the UEA team have discovered how a ferritin in one particular marine bacterium succeeds in carrying out this detoxification process.

Unusually, the bacterium produces the ferritin in response to high levels of copper, not iron. The team discovered that there was no direct interaction between the ferritin and the copper, but instead the ferritin catalysed a new kind of reaction between oxygen and iron. This generated a form of the ferritin that has an enhanced ability to detoxify ROS directly, whilst also carrying out its iron storage and detoxification roles.

Nick Le Brun, Professor of Biological Chemistry at UEA explains: “We believe the iron involved in this new pathway has been displaced from other iron-containing proteins by the copper, and the bacterium manages the toxicity of the displaced iron by producing the ferritin. This of particular interest because the ferritin involved more closely resembles those in animals than in other bacteria.”

This type of process has not previously been spotted by scientists and confirms that there are many different ferritin mechanisms at work across different organisms.

A search of genomic databases carried out by the team also revealed that many other similar marine bacteria may produce similar ferritins under conditions of stress. The team now plan to expand their research to investigate how widespread the new mechanism is.

“None of the previously studied ferritins, or indeed iron enzymes in general, react in the way this newly discovered ferritin does,” adds Professor Le Brun. “This novel chemistry not only represents a breakthrough for our understanding of natural anti-oxidant processes, it also reveals new possibilities for future engineered biocatalysts that could, for example, find use in drug development.”

The research was funded by the Biotechnology and Biological Sciences Research Council and is published today in PNAS.