Funded in part by Daiichi Sankyo Foundation of Life Science, Daiichi Sankyo Europe
Synergistic action of dendritic mitochondria and creatine kinase maintains ATP homeostasis and actin dynamics in growing neuronal dendrites
Fukumitsu K, Fujishima K, Yoshimura A, Wu YK, Heuser J, Kengaku M
The Journal of neuroscience : the official journal of the Society for Neuroscience · 75 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Industry funded
- Company
- Daiichi Sankyo Foundation of Life Science
- Government
- Japan Society for the Promotion of Science
- Company
- Daiichi Sankyo Europe
- Grants
- Japan Society for the Promotion of Science (25830011); Japan Society for the Promotion of Science (26290005)
Based on 3 listed funder(s).
Publication
- Published
- 2015-04-08 · J Neurosci · vol. 35 · issue 14 · pp. 5707–5723
- Publisher
- Society for Neuroscience
- Cited
- 83 citations · more than 95% of similar papers · 4.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 78 works
- Access
- Open access (hybrid journal) · CC-BY-NC-SA
- Research areas
- Neuroscience and Neuropharmacology Research · Mitochondrial Function and Pathology · Retinal Development and Disorders
- Keywords
- Mitochondrion, Cell biology, Cofilin, Phosphocreatine, Cytosol, Biology, Dendritic spine, Dendrite (mathematics), Actin remodeling of neurons, Cytoskeleton, Chemistry, Actin cytoskeleton, Neuroscience, Biochemistry, Cell
- MeSH
- cerebellum, hippocampus, neurons, dendrites, cells, cultured, mitochondria, animals, mice, inbred icr, humans, mice, dependovirus, egtazic acid, actins, creatine kinase, deoxyglucose, carrier proteins, luminescent proteins, nerve tissue proteins, adenosine triphosphate, calcium channel blockers, chelating agents, pregnancy, female, male, membrane potential, mitochondrial
6 authors
From JP, US
- Kansai FukumitsuKyoto University; Material Sciences (United States)
- Kazuto FujishimaMaterial Sciences (United States)
- Azumi YoshimuraMaterial Sciences (United States)
- You Kure WuKyoto University; Material Sciences (United States)
- John HeuserMaterial Sciences (United States)
- Mineko KengakuKyoto University; Material Sciences (United States)
Abstract
The distribution of mitochondria within mature, differentiated neurons is clearly adapted to their regional physiological needs and can be perturbed under various pathological conditions, but the function of mitochondria in developing neurons has been less well studied. We have studied mitochondrial distribution within developing mouse cerebellar Purkinje cells and have found that active delivery of mitochondria into their dendrites is a prerequisite for proper dendritic outgrowth. Even when mitochondria in the Purkinje cell bodies are functioning normally, interrupting the transport of mitochondria into their dendrites severely disturbs dendritic growth. Additionally, we find that the growth of atrophic dendrites lacking mitochondria can be rescued by activating ATP-phosphocreatine exchange mediated by creatine kinase (CK). Conversely, inhibiting cytosolic CKs decreases dendritic ATP levels and also disrupts dendrite development. Mechanistically, this energy depletion appears to perturb normal actin dynamics and enhance the aggregation of cofilin within growing dendrites, reminiscent of what occurs in neurons overexpressing the dephosphorylated form of cofilin. These results suggest that local ATP synthesis by dendritic mitochondria and ATP-phosphocreatine exchange act synergistically to sustain the cytoskeletal dynamics necessary for dendritic development.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-SA).
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