The axonal transport of mitochondria - PubMed (original) (raw)
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The axonal transport of mitochondria
Peter J Hollenbeck et al. J Cell Sci. 2005.
Abstract
Organelle transport is vital for the development and maintenance of axons, in which the distances between sites of organelle biogenesis, function, and recycling or degradation can be vast. Movement of mitochondria in axons can serve as a general model for how all organelles move: mitochondria are easy to identify, they move along both microtubule and actin tracks, they pause and change direction, and their transport is modulated in response to physiological signals. However, they can be distinguished from other axonal organelles by the complexity of their movement and their unique functions in aerobic metabolism, calcium homeostasis and cell death. Mitochondria are thus of special interest in relating defects in axonal transport to neuropathies and degenerative diseases of the nervous system. Studies of mitochondrial transport in axons are beginning to illuminate fundamental aspects of the distribution mechanism. They use motors of one or more kinesin families, along with cytoplasmic dynein, to translocate along microtubules, and bidirectional movement may be coordinated through interaction between dynein and kinesin-1. Translocation along actin filaments is probably driven by myosin V, but the protein(s) that mediate docking with actin filaments remain unknown. Signaling through the PI 3-kinase pathway has been implicated in regulation of mitochondrial movement and docking in the axon, and additional mitochondrial linker and regulatory proteins, such as Milton and Miro, have recently been described.
Figures
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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References
- Amaratunga A, Morin PJ, Kosik KS, Fine RE. Inhibition of kinesin synthesis and rapid anterograde axonal transport in vivo by an antisense oligonucleotide. J. Biol. Chem. 1993;268:17427–17430. - PubMed
- Amaratunga A, Leeman SE, Kosik KS, Fine RE. Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three transport vesicle classes into the axon. J. Neurochem. 1995;64:2374–2376. - PubMed
- Asai DJ, Wilkes DE. The dynein heavy chain family. J. Eukaryot. Microbiol. 2004;51:23–29. - PubMed
- Baas PW. Microtubule transport in the axon. Int. Rev. Cytol. 2002;212:41–62. - PubMed
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