Research reveals how succinate dehydrogenase is linked to both tumor and neurodegeneration

Prof. Sarah Fendt (VIB-KU Leuven): "In this project we have studied mutations in the enzyme succinate dehydrogenase, which are associated with tumors, but also neurodegeneration. This is per se already interesting, because tumors are defined by cells that show sustained proliferation and in this sense sustained fitness, while neurodegeration is defined by cells of impaired fitness. Thus, it is surprising that mutations in one and the same enzyme, which all lead to loss of enzyme expression result in two very distinct disease phenotypes."

Dr. Doriane Lorendeau (VIB-KU Leuven): "We now found that in succinate dehydrogenase mutations that lead to tumors an additional loss of complex I of the respiratory chain occurs and that the metabolic phenotype that is described for tumors with succinate dehydrogenase mutation requires the dual loss succinate dehydrogenase and complex I. In line, neurodegeneration defined by succinate dehydrogenase mutations does not lead to loss of complex I and thus results in a metabolically different phenotype, which can explain the impaired cellular fitness."

More information:
Doriane Lorendeau et al, Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors, Metabolic Engineering (2016). DOI: 10.1016/j.ymben.2016.11.005

Provided by VIB (the Flanders Institute for Biotechnology)