Mitochondria are one of the key players in cellular calcium signaling. Upon an increase in cytoplasmic calcium concentration, the mitochondrial calcium uniporter protein complex is activated allowing calcium to enter the mitochondrial matrix. Mitochondrial calcium entry is critical to a plethora of cellular processes including cytoplasmic calcium buffering, regulation of ATP production, apoptosis and autophagy (Kamer and Mootha, 2015).
Components of the mitochondrial calcium handling machinery were found among the hits of a pan-neuronal RNAi screen performed to discover new genes that are required for normal olfactory memory formation in Drosophila (Walkinshaw et al., 2015). Subsequent olfactory conditioning experiments showed that inhibiting mitochondrial calcium entry specifically in the mushroom bodies (MB) causes a memory impairment without altering the ability of the flies to learn. Surprisingly, impairing mitochondrial calcium entry in MB only during pupariation -but not during earlier developmental stages or adulthood- recapitulates the phenotype observed when mitochondrial calcium entry is impaired both during development and adulthood. Global structural analyses of the MB in flies where the mitochondrial calcium uniporter is silenced failed to reveal any gross structural defect. Nevertheless, a more detailed analysis revealed that the number of synaptic vesicles in the MB of these flies is significantly decreased when compared to control flies. Moreover, single MB neuron analyses using photoactivatable GFP showed that the axonal length of a specific sub-population of MB neurons is increased when mitochondrial calcium entry is inhibited.
Our results uncover a novel role for mitochondria calcium handling in vivo and reveal a relationship between developmental mitochondrial calcium homeostasis, olfactory memory formation, and MB neuronal structure in adult flies.