Metaxins are core components of mitochondrial transport adaptor complexes

Trafficking of mitochondria into dendrites and axons plays an important role in the physiology and pathophysiology of neurons. Mitochondrial outer membrane protein Miro and adaptor proteins TRAKs/Milton link mitochondria to molecular motors. Here we show that metaxins MTX-1 and MTX-2 contribute to mitochondrial transport into both dendrites and axons of C. elegans neurons. MTX1/2 bind to MIRO-1 and kinesin light chain KLC-1, forming a complex to mediate kinesin-1-based movement of mitochondria, in which MTX-1/2 are essential and MIRO-1 plays an accessory role. We find that MTX-2, MIRO-1, and TRAK-1 form another distinct adaptor complex to mediate dynein-based transport. Additionally, we show that failure of mitochondrial trafficking in dendrites causes age-dependent dendrite degeneration. We propose that MTX-2 and MIRO-1 form the adaptor core for both motors, while MTX-1 and TRAK-1 specify each complex for kinesin-1 and dynein, respectively. MTX-1 and MTX-2 are also required for mitochondrial transport in human neurons, indicative of their evolutionarily conserved function.