Comprehensive Genetic Characterization of Mitochondrial Ca²⁺ Uniporter Components Reveals Their Different Physiological Requirements In Vivo.

ABSTRACT: 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 characterization of all known uniporter components conserved in Drosophila. While loss of pore-forming MCU or EMRE abolishes fast mitochondrial Ca²⁺ 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 Ca²⁺ uptake. Mutants for the neuronally restricted regulator MICU3 are viable with mild neurological impairment. Genetic interaction analyses reveal that MICU1 and

SUBMITTER: Tufi R 

PROVIDER: S-EPMC6506686 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature