PUBLICATION
Retrograde mitochondrial transport is essential for organelle distribution and health in zebrafish neurons
- Authors
- Mandal, A., Wong, H.C., Pinter, K., Mosqueda, N., Beirl, A., Lomash, R.M., Won, S., Kindt, K.S., Drerup, C.M.
- ID
- ZDB-PUB-210101-5
- Date
- 2020
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 41(7): 1371-1392 (Journal)
- Registered Authors
- Beirl, Alisha, Wong, Hiu-Tung Candy
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Axonal Transport/physiology*
- Axons/metabolism*
- Axons/pathology
- Cells, Cultured
- Mitochondria/genetics
- Mitochondria/metabolism*
- Mitochondria/pathology
- Neurodegenerative Diseases/genetics
- Neurodegenerative Diseases/metabolism*
- Neurodegenerative Diseases/pathology
- Neurons/metabolism*
- Neurons/pathology
- Organelles/genetics
- Organelles/metabolism
- Organelles/pathology
- Rats
- Zebrafish
- PubMed
- 33376159 Full text @ J. Neurosci.
Citation
Mandal, A., Wong, H.C., Pinter, K., Mosqueda, N., Beirl, A., Lomash, R.M., Won, S., Kindt, K.S., Drerup, C.M. (2020) Retrograde mitochondrial transport is essential for organelle distribution and health in zebrafish neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 41(7):1371-1392.
Abstract
In neurons, mitochondria are transported by molecular motors throughout the cell to form and maintain functional neural connections. These organelles have many critical functions in neurons and are of high interest as their dysfunction is associated with disease. While the mechanics and impact of anterograde mitochondrial movement towards axon terminals is beginning to be understood, the frequency and function of retrograde (cell body directed) mitochondrial transport in neurons is still largely unexplored. While existing evidence indicates that some mitochondria are retrogradely transported for degradation in the cell body, the precise impact of disrupting retrograde transport on the organelles and the axon was unknown. Using long-term, in vivo imaging we examined mitochondrial motility in zebrafish sensory and motor axons. We show that retrograde transport of mitochondria from axon terminals allows replacement of the axon terminal population within a day. By tracking these organelles, we show that not all mitochondria that leave the axon terminal are degraded; rather, they persist over several days. Disrupting retrograde mitochondrial flux in neurons leads to accumulation of aged organelles in axon terminals and loss of cell body mitochondria. Assays of neural circuit activity demonstrated that disrupting mitochondrial transport and function has no effect on sensory axon terminal activity but does negatively impact motor neuron axons. Taken together, our work supports a previously unappreciated role for retrograde mitochondrial transport in the maintenance of a homeostatic distribution of mitochondria in neurons and illustrates the downstream effects of disrupting this process on sensory and motor circuits.SIGNIFICANCE STATEMENTDisrupted mitochondrial transport has been linked to neurodegenerative disease. Retrograde transport of this organelle has been implicated in turnover of aged organelles through lysosomal degradation in the cell body. Consistent with this, we provide evidence that retrograde mitochondrial transport is important for removing aged organelles from axons; however, we show that these organelles are not solely degraded, rather they persist in neurons for days. Disrupting retrograde mitochondrial transport impacts the homeostatic distribution of mitochondria throughout the neuron and the function of motor, but not sensory, axon synapses. Together, our work shows the conserved reliance on retrograde mitochondrial transport for maintaining a healthy mitochondrial pool in neurons and illustrates the disparate effects of disrupting this process on sensory verses motor circuits.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping