Fig. 1. Key components of the Motor-adaptor-receptor complex for intracellular mitochondrial movement.

Axonal microtubule (MT) are uniformly arranged with their plus end (+end) directed distally and minus end (−end) towards soma. (A) Plus-end directed anterograde transport (−end to +end) of mitochondria is mediated by the Kinesin motor. The N-terminal domain the motor domain with ATPase activity and binds directly the MT. The C-terminal is the cargo binding domain. Milton (or TRAK1/2) is the motor adaptor protein that links Miro (present in the outer mitochondrial membrane) to the cargo binding domain of Kinesin. (B) Minus-end directed retrograde transport (+end to −end) of mitochondria is mediated by the cytoplasmic MT-based dynein motor. Dynein contains multiple subunits including two catalytic heavy chains (DHC), several intermediate chains (DIC) and light chains (DLC). DHC is the motor domain required for dynein movement. Dynactin is a large protein complex that interacts with dynein and MT through the p150^Glued subunit. Both dynein and dynactin together drive the retrograde mitochondrial movement. (C and D) Actin filament based short distance mitochondrial transport is mediated by myosin. Myosin is a two-headed motor protein with a unique globular tail domain that can interact directly with kinesin motor (C), or with DLC (D) raising the possibility of this motor to facilitate both long-range transport along MT and short-distance transport along actin filaments. (E) Myo19 was identified as the mitochondria associated myosin. Myo19 directly interacts with Miro through its C-terminal fragment of the tail region.