Scientists have found that acute myeloid leukaemia (AML) cells change the shape of their mitochondria to avoid the effect of the drug venetoclax, which triggers cell suicide. These changes are controlled by the OPA1 protein, which causes the inner folds of the mitochondria (cristae) to become tighter and more numerous. In patients who relapsed after treatment with venetoclax, the mitochondrial cristae were the tightest. In mouse experiments with human AML cells, blocking OPA1 inhibitors together with venetoclax was shown to increase survival by at least twofold compared with venetoclax alone. These results suggest that alteration of mitochondrial shape is a key mechanism of drug resistance. Blocking OPA1 may be a novel strategy to overcome venetoclax resistance. The studies used electron microscopy and genetic analyses to confirm the mechanism.