PINK1/parkin are key mediators of stress-induced mitophagy in vitro, but their impact on basal mitophagy in vivo is unclear. Novel Drosophila reporter lines reveal abundant mitophagy in many tissues, including dopaminergic neurons, that is unaffected by loss of PINK1/parkin.

Summary Mitochondrial Ca 2+ uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca 2+ uniporter has opened it up to genetic analysis in model organisms. Here, we report a comprehensive genetic characterization of all known uniporter components conserved in Drosophila . While loss of pore-forming MCU or EMRE abolishes fast mitochondrial Ca 2+ uptake, this results in only mild phenotypes when young, despite shortened lifespans. In contrast, loss of the MICU1 gatekeeper is developmentally lethal, consistent with unregulated Ca 2+ uptake. Mutants for the neuronally restricted regulator MICU3 are viable with mild neurological impairment. Genetic interaction analyses reveal that MICU1 and MICU3 are not functionally interchangeable. More surprisingly, loss of MCU or EMRE does not suppress MICU1 mutant lethality, suggesting that this results from uniporter-independent functions. Our data reveal the interplay among components of the mitochondrial Ca 2+ uniporter and shed light on their physiological requirements in vivo .