A study led by Dr James Nathan (Cambridge Institute for Medical Research, Department of Medicine) has demonstrated the influence of a novel metabolic pathway on the oxygen sensing machinery in cells. Published in Cell Metabolism, they show that the Oxoglutarate Dehydrogenase Complex – a key enzyme involved in mitochondrial respiration, controls the level of a metabolite L-2-hydroxyglutarate (L-2-HG) which directly alters the activity of oxygen sensing enzymes.
This work, with Dr Stephen Burr as first author and in collaboration with scientists from the MRC Cancer Unit, CIMR, and Department of Medicine, also found that children with mutations in genes affecting this mitochondrial complex activate a transcriptional response that is usually only observed when cells are exposed to low oxygen.
These studies reveal a fundamental link between metabolism and oxygen sensing enzymes, and given that L-2-HG is emerging as an ‘oncometabolite’ which promotes tumour formation, will have broad implications for the understanding of cancer biology.
