Mystery of human energy solved by MRC scientists
13 March 2006
Scientists at the Medical Research Council have unravelled one of the final puzzles in explaining how the body produces energy. The discovery, published in the journal Science, has helped to explain the rate of human ageing and has implications for future research into medical therapies for diseases including Parkinson’s and age-related disorders.
Inside cells there are biological power stations, called mitochondria, which generate energy. The problem was working out how mitochondria produce energy. Scientists knew that five enzymes in the membrane of the mitochondria produced energy and had worked out the structure of four of them. Now a team at the Medical Research Council Dunn Human Nutrition Unit in Cambridge has determined the structure of a major part of the fifth and most complicated enzyme, known as Complex I.
Several laboratories around the world have been trying to crack the riddle of this complex. The MRC team, led by Dr. Leonid Sazanov, is the first to do it.
Speaking about the potential benefits of his research, Dr Sazanov said: “One of the many new revelations from the structure is related to ageing. We now know how elegantly different elements of the complex are arranged, so that electrons can be transferred through the complex with maximum effectiveness and minimal “leak” into surroundings. If this “leak” were higher, more oxygen radicals would be produced, which can damage DNA and may lead to accelerated ageing.”
He went on to explain that the discovery may help work out new ways to understand the ageing process, which could eventually lead to better treatments: “Knowing the structure may suggest ways to minimize even more the production of damaging radicals, with implications for dealing with ageing. It is also clear now how the complex is assembled from many smaller proteins, which act as “building blocks” and fit together perfectly as pieces of a jigsaw puzzle.”
This work builds on research carried out by Sir John Walker, director of the MRC Dunn Human Nutrition Unit, who won the Nobel prize in 1997. Sir John said: “Leo Sazanov is on the way to solving a piece of fundamental science which is a central issue in biology. Mutations in the DNA of this enzyme have been linked to muscle and nerve degeneration in diseases like Parkinson’s. We still have work to do to understand fully this structure but it will eventually lead to treatments and drugs. There is a lot of medical mileage in this work.”
