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Cited by 24Cellular transport and secretionAutophagy in Disease and TherapyExtracellular vesicles in disease

Intracellular redistribution of neuronal peroxisomes in response to ACBD5 expression

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Wang, Yunhong, Metz, Jeremy, Costello, Joseph L., Passmore, Josiah, Schrader, Michael, Schultz, Christian, Islinger, Markus·2018·PLOS ONE
DOI 10.1371/journal.pone.0209507PMC PMC6307868
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Abstract

Peroxisomes can be frequently found in proximity to other subcellular organelles such as the endoplasmic reticulum (ER), mitochondria or lysosomes. The tail-anchored protein ACBD5 was recently identified as part of a tethering complex at peroxisome-ER contact sites, interacting with the ER resident protein VAPB. Contact site disruption was found to significantly increase peroxisome motility, apparently interfering with intracellular positioning systems. Unlike other somatic cells, neurons have to distribute organelles across relatively long distances in order to maintain their extraordinary cellular polarity. Using confocal live imaging microscopy in cultured hippocampal neurons we observed that peroxisomes and mitochondria show a strikingly similar motility with approximately 10% performing microtubule-driven long range movements. In order to investigate if ER contacts influence overall peroxisome motility and cellular distribution patterns, hippocampal neurons were transfected with plasmids encoding ACBD5 to stimulate peroxisome-ER interactions. Overexpression of ACBD5 reduced peroxisomal long range movements in the neurites of the hippocampal cells by 70%, implying that ER attachment counteracts microtubule-driven peroxisome transport, while mitochondrial motility was unaffected. Moreover, the analyses of peroxisome distribution in fixed neurons unveiled a significant redistribution of peroxisomes towards the periphery of the perikaryon underneath the plasma membrane and into neurites, where peroxisomes are frequently found in close proximity to mitochondria. Surprisingly, further analysis of peroxisome and VAPB distribution upon ACBD5 expression did not reveal a substantial colocalization, implying this effect may be independent of VAPB. In line with these findings, expression of an ACBD5 variant unable to bind to VAPB still altered the localization of peroxisomes in the same way as the wild-type ACBD5. Thus, we conclude, that the VAPB-ACBD5 facilitated peroxisome-ER interaction is not responsible for the observed organelle redistribution in neurons. Rather, we suggest that additional ACBD5-binding proteins in neurons may tether peroxisomes to contact sites at or near the plasma membrane of neurons.

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  • Peroxisomes are few in neuron perikarya or dendrites, rare within axons, and absent in synaptic terminals in the spinal cord except during early development.

    “While mitochondria fill dendrites and axons, peroxisomes are few in neuron perikarya or dendrites, rare within axons [251,253,254,255,292,293], and absent in synaptic terminals in the spinal cord [255] except during early development [255].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [293]

    The Introduction says peroxisomes are virtually absent from axons in mature projection neurons and accumulate in axon terminals during early postnatal development. It does not establish that they are few in perikarya or dendrites. The spinal-cord-specific statement is attached to a different citation in the citing sentence and is not assessed against this paper. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Wang, Y., Metz, J., Costello, J. L., Passmore, J., Schrader, M., Schultz, C., & Islinger, M.
Affiliations
  • University of Exeter (GB)
  • Heidelberg University (DE)
Corresponding author
Islinger, Markus
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-12-27
Volume
13
Issue
12
Pages
e0209507
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0209507
PMC
PMC6307868
OpenAlex
W2907673292
Cited by
24
References
2
Citations by year
2026: 1 · 2025: 7 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 6 · 2019: 1
FWCI
1.11
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (397476530, D10043030)
  • Biotechnology and Biological Sciences Research Council (BB/K006231/1, BB/N01541X/1)
  • Welcome Trust Institutional Strategic Support Award (WT097835MF, WT105618MA)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
peroxisomes, VAPB, mitochondrial motility, neuronal polarity, neurites, hippocampal neurons
MeSH terms
Intravital Microscopy, Animals, Cells, Cultured, Embryo, Mammalian, Endoplasmic Reticulum, Female, Hippocampus, Membrane Proteins, Mice, Inbred C57BL, Neurons, Microscopy, Confocal, Peroxisomes, Vesicular Transport Proteins, Adaptor Proteins, Signal Transducing, Mitochondrial Membranes, Mice, Primary Cell Culture

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