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ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila
Mitochondria perform critical functions including aerobic ATP production and calcium (Ca(2+)) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regio...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436889/ https://www.ncbi.nlm.nih.gov/pubmed/28542430 http://dx.doi.org/10.1371/journal.pone.0178105 |
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author | Liao, Pin-Chao Tandarich, Lauren C. Hollenbeck, Peter J. |
author_facet | Liao, Pin-Chao Tandarich, Lauren C. Hollenbeck, Peter J. |
author_sort | Liao, Pin-Chao |
collection | PubMed |
description | Mitochondria perform critical functions including aerobic ATP production and calcium (Ca(2+)) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using the Drosophila third instar larval nervous system as the in vivo model, we found that ROS inhibited mitochondrial axonal transport more specifically, primarily due to reduced flux and velocity, but did not affect transport of other organelles. To understand the mechanisms underlying these effects, we examined Ca(2+) levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca(2+) levels, and that experimental reduction of Ca(2+) to physiological levels rescued ROS-induced defects in mitochondrial transport in primary neuron cell cultures. In addition, in vivo activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca(2+) and JNK signaling play roles in mediating these effects. In addition to transport defects, ROS produces imbalances in mitochondrial fission-fusion and metabolic state, indicating that mitochondrial transport, fission-fusion steady state, and metabolic state are closely interrelated in the response to ROS. |
format | Online Article Text |
id | pubmed-5436889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54368892017-05-27 ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila Liao, Pin-Chao Tandarich, Lauren C. Hollenbeck, Peter J. PLoS One Research Article Mitochondria perform critical functions including aerobic ATP production and calcium (Ca(2+)) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using the Drosophila third instar larval nervous system as the in vivo model, we found that ROS inhibited mitochondrial axonal transport more specifically, primarily due to reduced flux and velocity, but did not affect transport of other organelles. To understand the mechanisms underlying these effects, we examined Ca(2+) levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca(2+) levels, and that experimental reduction of Ca(2+) to physiological levels rescued ROS-induced defects in mitochondrial transport in primary neuron cell cultures. In addition, in vivo activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca(2+) and JNK signaling play roles in mediating these effects. In addition to transport defects, ROS produces imbalances in mitochondrial fission-fusion and metabolic state, indicating that mitochondrial transport, fission-fusion steady state, and metabolic state are closely interrelated in the response to ROS. Public Library of Science 2017-05-18 /pmc/articles/PMC5436889/ /pubmed/28542430 http://dx.doi.org/10.1371/journal.pone.0178105 Text en © 2017 Liao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Liao, Pin-Chao Tandarich, Lauren C. Hollenbeck, Peter J. ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title | ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title_full | ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title_fullStr | ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title_full_unstemmed | ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title_short | ROS regulation of axonal mitochondrial transport is mediated by Ca(2+) and JNK in Drosophila |
title_sort | ros regulation of axonal mitochondrial transport is mediated by ca(2+) and jnk in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436889/ https://www.ncbi.nlm.nih.gov/pubmed/28542430 http://dx.doi.org/10.1371/journal.pone.0178105 |
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