Understanding an 'ageing enzyme'

The structure of a key energy-releasing enzyme found in all animals is designed to minimise free radical production, an international team of researchers has revealed.

In a startling feat of structural biology, the team visualised the entire molecular structure of the protein succinate dehydrogenase in the bacterium E.coli, allowing them to see for the first time how its three-dimensional (3D) shape helps prevent the formation of large quantities of the destructive free radical oxygen atoms.

Formed as a by-product during cellular respiration, these can cause havoc in cells by reacting with DNA or the cell membrane, knocking out or impairing their function, a process linked to cellular ageing.

Some of the key research in this discovery was carried out by a team at Imperial College, London (ICL) led by Professor So Iwata.

Professor Paul Fremont, the director of ICL's Centre for Structural Biology, said, "Professor Iwata's group has performed an extraordinary feat in obtaining the first three-dimensional insights of succinate dehydrogenase.

"This fundamentally important and highly complex metabolic enzyme protects the bacterium from self-inflicted damage and lies at the heart of the cell's energy powerhouse. It acts as a built-in anti-pollution system and has significant implications for understanding human ageing."

Prof. Iwata said, "Solving the structure of succinate dehydrogenase opens up new leads in the quest to understand longevity and ageing. It now appears that a wide variety of genetic disorders - including muscle and neurodegenerative diseases, and tumour formation - are caused by defective forms of this enzyme as a result of increased free radical formation.

"The challenge now is to try and engineer succinate dehydrogenase to maximise its efficiency. The E.coli bacterium provides a flexible model to advance this research because the enzyme is very similar to the human version."

Succinate dehydrogenase plays a key part in a process known as cellular respiration which oxidises food molecules such as glucose to release energy for use in the body when oxygen is present. Embedded in the inner membrane of the mitochondria, the enzyme is involved in a system that transfers energy using electrons.