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Piston engine helps to explain energy production within cells

27 May 2010

 

Medical Research Council (MRC) scientists have identified the structure of the vital enzyme ‘respiratory complex I’, solving a key part of the puzzle of how our cells gain energy from food. This discovery opens up new avenues of research into future treatments for neuromuscular diseases and for neurodegenerative diseases such as Parkinson’s. An image of this L-shaped enzyme features on the cover of today’s edition of Nature.

 

‘Respiratory complex I’ is the first in a set of molecular ‘machines’ in mitochondria that convert energy in food into a form that can be used by cells. Mitochondria have been described as the ‘power stations’ inside our cells.

 

As the gateway for cellular energy production, this enzyme is vital for the survival of most cells in our bodies.  However it also creates chemical by-products such as hydrogen peroxide, which can damage the DNA inside mitochondria. This damage accumulates during our lives and is likely to contribute to ageing and to neurodegenerative diseases such as Parkinson’s.

 

By increasing our understanding of the exact nature of how this enzyme works within cells, researchers will find it easier to identify when and where significant damage is most likely to happen, potentially leading to new options for treatment.

 

Dr Sazanov and his team at the MRC Mitochondrial Biology Unit had previously established the detailed structure of half of this enzyme with its distinctive L-shape. However, it took this most recent study for them to understand fully that its action appears to mimic that of a piston-driven steam engine, using an up and down motion to drive protons or ‘fuel’ across the mitochondrial membrane barrier.

 

Lead author, Dr Leonid Sazanov of the Medical Research Council, said: “Determining the structure of ‘respiratory complex I’ will help us to better understand how the enzyme works at a fundamental level. Until now this has been a real mystery to researchers in the field, including those working towards limiting the damage to mitochondrial DNA in our cells and curbing the vicious effects of neurodegenerative diseases. As a scientist, I admit that I also find it very satisfying that one of the most efficient and elegant processes in the body bears a striking resemblance to one of the great man-made inventions.”

 

This study complements a previous discovery by MRC researcher Professor Sir John Walker, Director of the MRC Mitochondrial Biology Unit, who determined that ‘respiratory complex V’, or ATP synthase, that carries out the final process in the biological energy production, is a rotary machine that resembles a turbine engine. Professor Walker was awarded the 1997 Nobel Prize in Chemistry for this work. 

 

ENDS

 

 

Notes to Editors:

  • 1. ‘The architecture of respiratory complex I’ is published in the journal Nature on 27 May 2010.
     
  • 2. This study took place at the MRC’s Mitochondrial Biology Unit, set up to explore how mitochondria work, how they reproduce themselves inside our cells and to study their role in human diseases.
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  • 3. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
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