Mitochondria are complex structures that exist in cells to generate energy for growth and activity.

The Cancer Research UK researchers based at the University of Glasgow's Beatson Institute for Cancer Research in Glasgow have found out how the excessive build-up of a simple metabolic molecule in mitochondria can trigger a sequence of events that leads to tumour growth.

The discovery increases our understanding of the molecular basis of several types of cancer, which is crucial for the development of new ways to prevent, diagnose and treat the disease.

Scientists know that a number of genes that code for the mitochondria's energy generating machinery are tumour suppressors and that defects in these genes can lead to cancer. But, until now, it was unclear as to how mutations in these genes resulted in the disease.

The team looked at one of the known tumour suppressor genes called SDH, which codes for a molecule called succinate dehydrogenase. When the SDH gene is damaged, a metabolic product called succinic acid accumulates in cells. This then causes the levels of a protein called HIF-1to rise. The HIF-1 protein is normally only activated in response to certain types of crisis in the cell, such as a lack of oxygen. Under these conditions it encourages the growth of blood vessels to help cells get more oxygen.

The researchers have found the missing pieces in this puzzle. They show how the high levels of succinic acid in the cell that result from SDH mutations block the cell's usual method of ridding the cell of HIF-1. HIF-1 levels can then build up, resulting in inappropriate growth of blood vessels, which can feed a tumour.

Dr. Eyal Gottlieb, from the University of Glasgow's Beatson Institute, said: "We found that dama
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Contact: Jenny Murray
jennifer.murray@admin.gla.ac.uk
University of Glasgow
31-Jan-2005