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Fig. 1. A summary framework for considering mechanisms that contribute to the transport and localization of mitochondria in axons. All three motor-protein families are likely to participate in moving axonal mitochondria. Kinesins and dynein, perhaps bound in the same motor complex or perhaps independently associated with mitochondria, drive long-range anterograde and retrograde transport. Mechanisms that coordinate those opposing motors to produce net transport in one direction are largely unknown, although the dynactin complex could be an important factor. Myosins drive short-range movements along F-actin, they may modulate long-range transport by pulling mitochondria away from microtubules, and they might facilitate anchorage of mitochondria to F-actin by unknown actin-mitochondrion crosslinkers. Possible control mechanisms that could regulate transport and docking are numerous and remain largely speculative. However, it is relatively certain that mitochondrial motors and anchors are controlled by phosphorylation/dephosphorylation and perhaps by other regulatory schemes. The regulatory pathways may include, but are certainly not limited to, CDK5/GSK3, NGF/PI3K, Abl/Ena/VASP, mitochondrial inner membrane potential and the levels of Ca2+ and Zn2+.
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