Moving or stopping mitochondria: Miro as a traffic cop by sensing calcium

Abstract

Mitochondrial transport in neurons and their spatial distribution among synapses are directly correlated with synaptic activity. One paper in this issue of Neuron (MacAskill et al.) and two papers recently published in Cell (Wang and Schwarz) and PNAS (Saotome et al.) provide compelling evidence that Miro serves as a calcium sensor that controls mitochondrial mobility.

Figure 1. Schematic Models of Miro as a Ca²⁺ Sensor in Regulating Mitochondrial Mobility

(A) Ca²⁺ binding detaches KIF5 from mitochondria. Mitochondrial transport is mediated by linking Miro to KIF5. Ca²⁺ binding to the EF hands dissociates Miro from KIF5 while KIF5-binding protein GRIF-1/TRAK2 (a mammalian homolog of milton) remains bound to Miro1 (MacAskill et al., 2008, 2009). (B) Ca²⁺ binding turns “off” KIF5 engagement with MTs. The tail of KIF5 is linked to Miro via milton in a Ca²⁺-independent manner, thus leaving its motor domain to engage with MTs. Ca²⁺ binding to the EF hands triggers the direct interaction of the motor domain with Miro, thus preventing the motor from engaging with MTs (Wang and Schwarz, 2009).