These mutations corrupt complex II’s electron transport activity, leading to succinate accumulation, increased ROS generation and decreased ATP production through oxidative phosphorylation (OXPHOS).56,57 The frequent loss of complex II subunit expression in cancer (in particular SDHB) suggests that these subunits might have tumour-suppressor functions; indeed, the accumulation of succinate activates the HIF-1α oncogenic pathway.58 This evidence concerns the gene HIF1A and cancer.