McBride and colleagues previously observed budding of two vesicle populations from mitochondria, one of which was targeted to peroxisomes. But the fate of the second vesicle pool was unclear. Here, they define the target destination for these vesicles as lysosomes, and thus elucidate a new vesicular transport route that might influence mitochondrial quality control, perhaps by eliminating oxidized complexes that accumulate during mitochondrial respiration. They find that vesicle budding and lysosomal targeting occur both at steady state and early during oxidative stress, and that the extent of budding correlates with the level of respiratory activity. There are several indications that this mitochondrion–lysosome transport pathway is independent of the mitochondrial fission and mitophagy pathways. The questions now are how cargo is selected for removal by these vesicles, and what kick-starts vesicle formation.