DOI: 10.1101/458174Oct 31, 2018Paper

A comprehensive genetic characterisation of the mitochondrial Ca2+ uniporter in Drosophila

BioRxiv : the Preprint Server for Biology
Roberta TufiAlexander Whitworth


Mitochondrial Ca2+ uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca2+ uniporter has opened it up to genetic analysis in model organisms. Here we report a comprehensive genetic characterisation of the known uniporter components conserved in Drosophila. While loss of MCU or EMRE abolishes fast mitochondrial Ca2+ uptake, this results in surprisingly mild phenotypes. In contrast, loss of the regulatory gatekeeper component MICU1 has a much more severe phenotype, being developmental lethal, consistent with unregulated Ca2+ uptake. Mutants for MICU3 are viable with mild neurological phenotypes. Genetic interaction studies reveal that MICU1 and MICU3 are not functionally interchangeable. More surprisingly, loss of MCU or EMRE does not suppress MICU1 mutant lethality, suggesting that the lethality results from MCU-independent functions. This study helps shed light on the physiological requirements of the mitochondrial Ca2+ uniporter, and provides a suite of tools to interrogate their interplay in homeostasis and disease conditions.

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