Scientists at the Medical Research Council (MRC), UK have identified the structure of the critical enzyme respiratory complex I, solving an important part of the puzzle of how our cells get their energy from food. This discovery will result in new avenues of research into future potential treatments for neuromuscular and neurodegenerative diseases, such as Parkinson’s.
Respiratory complex I is the first in a set of molecular ‘machines’ in mitochondria that transform energy in food into a form that can be utilized by cells. Mitochondria are the ‘power stations’ inside our cells.
As the first stage for cellular energy production, this enzyme is critical for the continued existence of the majority of cells in our bodies. However, it also creates chemical by-products, such as H2O2 (hydrogen peroxide), a strongly oxidizing liquid which can damage the DNA within the mitochondria. This damage builds up during a human’s life and probably contributes to ageing and to neurodegenerative diseases, such as Parkinson’s.
By better understanding exactly how this enzyme works within cells, scientists will be able to identify when and where significant damage is likely to happen, hopefully resulting in new treatment options.
Dr Sazanov and team at the MRC (Medical Research Council) 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 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.
In a previous study, Professor Sir John Walked, Director of the MRC Mitochondrial Biology Unit, had 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.
Rouslan G. Efremov, Rozbeh Baradaran, Leonid A. Sazanov
Nature Volume:465, Pages: 441-445
DOI: doi:10.1038/nature09066
Written by Christian Nordqvist