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Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits
Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhance...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932375/ https://www.ncbi.nlm.nih.gov/pubmed/27268498 http://dx.doi.org/10.1083/jcb.201605101 |
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author | Zhou, Bing Yu, Panpan Lin, Mei-Yao Sun, Tao Chen, Yanmin Sheng, Zu-Hang |
author_facet | Zhou, Bing Yu, Panpan Lin, Mei-Yao Sun, Tao Chen, Yanmin Sheng, Zu-Hang |
author_sort | Zhou, Bing |
collection | PubMed |
description | Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration. |
format | Online Article Text |
id | pubmed-4932375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49323752017-01-04 Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits Zhou, Bing Yu, Panpan Lin, Mei-Yao Sun, Tao Chen, Yanmin Sheng, Zu-Hang J Cell Biol Research Articles Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration. The Rockefeller University Press 2016-07-04 /pmc/articles/PMC4932375/ /pubmed/27268498 http://dx.doi.org/10.1083/jcb.201605101 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Zhou, Bing Yu, Panpan Lin, Mei-Yao Sun, Tao Chen, Yanmin Sheng, Zu-Hang Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title | Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title_full | Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title_fullStr | Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title_full_unstemmed | Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title_short | Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
title_sort | facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932375/ https://www.ncbi.nlm.nih.gov/pubmed/27268498 http://dx.doi.org/10.1083/jcb.201605101 |
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