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Sci Rep. 2016 Jun 20;6:28331. doi: 10.1038/srep28331.

Mitochondrial fission is an acute and adaptive response in injured motor neurons.

Author information

1
Department of Functional Anatomy and Neuroscience, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
2
CREST, JST, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
3
Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
4
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University,Fukuoka 812-8382, Japan.
5
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8382, Japan.

Abstract

Successful recovery from neuronal damage requires a huge energy supply, which is provided by mitochondria. However, the physiological relevance of mitochondrial dynamics in damaged neurons in vivo is poorly understood. To address this issue, we established unique bacterial artificial chromosome transgenic (BAC Tg) mice, which develop and function normally, but in which neuronal injury induces labelling of mitochondria with green fluorescent protein (GFP) and expression of cre recombinase. GFP-labelled mitochondria in BAC Tg mice appear shorter in regenerating motor axons soon after nerve injury compared with mitochondria in non-injured axons, suggesting the importance of increased mitochondrial fission during the early phase of nerve regeneration. Crossing the BAC Tg mice with mice carrying a floxed dynamin-related protein 1 gene (Drp1), which is necessary for mitochondrial fission, ablates mitochondrial fission specifically in injured neurons. Injury-induced Drp1-deficient motor neurons show elongated or abnormally gigantic mitochondria, which have impaired membrane potential and axonal transport velocity during the early phase after injury, and eventually promote neuronal death. Our in vivo data suggest that acute and prominent mitochondrial fission during the early stage after nerve injury is an adaptive response and is involved in the maintenance of mitochondrial and neuronal integrity to prevent neurodegeneration.

PMID:
27319806
PMCID:
PMC4913268
DOI:
10.1038/srep28331
[Indexed for MEDLINE]
Free PMC Article

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