(A) Schematic diagram of Miro1‘s functional domains, which consist of two GTPase domains flanking two Ca²⁺-binding EF-hand domains. Miro1 also has an outer-mitochondrial transmembrane domain. (B) Under basal conditions, Miro1 forms a complex with TRAK1/TRAK2 and KIF5. This complex binds the microtubule network and allows anterograde transport. As well as binding kinesins, Miro1 can bind dynein motors via TRAK2 and this instead allows retrograde transport. During activity there is a concomitant influx of Ca²⁺, which binds to Miro1 causing a conformational change in its structure resulting in its uncoupling from the transport network. Upon uncoupling, mitochondria are rendered immobile and in this way they are retained at sites of high Ca²⁺. Three possible models have been proposed for the uncoupling of Miro1 from the microtubule network. (i) KIF5 remains bound to the microtubule network [40], (ii) KIF5 remains bound to the Miro1/TRAK2 complex upon uncoupling [55], or (iii) detachment from KIF5 occurs with subsequent interaction of the mitochondrial tether syntaphilin (SNPH) [61].