Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.
Hiromi TamadaSumiko Kiryu-SeoHiroki HosokawaKeisuke OhtaNaotada IshiharaMasatoshi NomuraKatsuyoshi MiharaKei-Ichiro NakamuraHiroshi KiyamaPublished in: The Journal of comparative neurology (2017)
Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation.
Keyphrases
- oxidative stress
- electron microscopy
- spinal cord
- cell death
- reactive oxygen species
- endoplasmic reticulum
- copy number
- quality control
- liver fibrosis
- high fat diet induced
- high glucose
- diabetic rats
- cerebral ischemia
- transcription factor
- high resolution
- gene expression
- deep learning
- spinal cord injury
- endoplasmic reticulum stress
- endothelial cells
- brain injury
- insulin resistance
- atrial fibrillation
- dna methylation
- optical coherence tomography
- subarachnoid hemorrhage
- blood brain barrier
- data analysis