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Mitochondrial Dynamics and Axonal Transport

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Mitochondrial Dynamics and Neurodegeneration

Abstract

Mitochondria are essential organelles for neuronal survival and function through ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport along axons to areas in which energy production and calcium homeostasis are in high demand, namely, active growth cones, nodes of Ranvier, and synaptic terminals. Axonal mitochondria display complex mobility patterns and undergo saltatory and bidirectional movement. While one-third of axonal mitochondria are mobile, the rest remains stationary. Docked mitochondria serve as local power plants and maintain local Ca2+ homeostasis. The balance between mobile and stationary mitochondria is influenced by the diverse physiological states of axons and synapses. The coordination of mitochondrial mobility by axonal physiology is crucial for neuronal development and synaptic function. Defects in mitochondrial transport have been implicated in the pathologic processes of several major neurodegenerative diseases. Thus, understanding the regulation of axonal mitochondrial transport will increase our knowledge of fundamental processes that may affect human neurological disorders. In this chapter, we introduce recent advances in our understanding of motor-adaptor complexes and docking machinery that mediate mitochondrial transport and axonal distribution. We will also discuss the molecular mechanisms underlying the complex mobility patterns of axonal mitochondria and how mitochondrial mobility impacts the physiology and function of synapses.

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Abbreviations

(MT):

Microtubule

(NF):

Neurofilament

(KIFs):

kinesin superfamily proteins

(KHC):

kinesin heavy chains

(KLC):

kinesin light chains

(DHC):

dynein heavy chains

(DIC):

dynein intermediate chains

(DLIC):

dynein light intermediate chains

(DLC):

dynein light chains

(dMiro):

drosophila mitochondrial Rho-GTPase

(TRAK1):

trafficking protein kinesin-binding 1

(FEZ1):

fasciculation and elongation protein zeta-1

(JIP1):

c-Jun N-terminal kinase (JNK)-interacting protein

(SNPH):

syntaphilin

(FCCP):

cyanide-p-trifluoromethoxyphenyhydrazone

(DRG):

dorsal root ganglion

(NO):

nitric oxide

(Mfn2):

mitofusin 2

(EPSCs):

excitatory postsynaptic currents

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Acknowledgements

We thank the members of the Sheng lab for helpful discussions and M. Davis for editing of the manuscript. The authors are supported by the Intramural Research Program of NINDS, NIH.

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  1. Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2B-215, 35 Convent Drive, Bethesda, MD, 20892–3706, USA

    Qian Cai & Zu-Hang Sheng

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  1. Qian Cai
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  2. Zu-Hang Sheng
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Correspondence to Zu-Hang Sheng .

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  1. , Department of Pathology, Stanford University School of Medicine, Allardice Way 825, Stanford, 94305, California, USA

    Bingwei Lu

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Cai, Q., Sheng, ZH. (2011). Mitochondrial Dynamics and Axonal Transport. In: Lu, B. (eds) Mitochondrial Dynamics and Neurodegeneration. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1291-1_5

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