Imperial College London
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ProfessorSimoneDi Giovanni

Faculty of Medicine, Department of Brain Sciences

James W Harnett Chair in Restorative Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 3178s.di-giovanni

 
 
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Location

 

E505Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Beck:2012:10.1073/pnas.1208141109,
author = {Beck, H and Flynn, K and Lindenberg, KS and Schwarz, H and Bradke, F and Di, Giovanni S and Knöll, B},
doi = {10.1073/pnas.1208141109},
journal = {Proceedings of the National Academy of Sciences},
title = {Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics},
url = {http://dx.doi.org/10.1073/pnas.1208141109},
volume = {109},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:p>Aberrant mitochondrial function, morphology, and transport are main features of neurodegenerative diseases. To date, mitochondrial transport within neurons is thought to rely mainly on microtubules, whereas actin might mediate short-range movements and mitochondrial anchoring. Here, we analyzed the impact of actin on neuronal mitochondrial size and localization. F-actin enhanced mitochondrial size and mitochondrial number in neurites and growth cones. In contrast, raising G-actin resulted in mitochondrial fragmentation and decreased mitochondrial abundance. Cellular F-actin/G-actin levels also regulate serum response factor (SRF)-mediated gene regulation, suggesting a possible link between SRF and mitochondrial dynamics. Indeed, SRF-deficient neurons display neurodegenerative hallmarks of mitochondria, including disrupted morphology, fragmentation, and impaired mitochondrial motility, as well as ATP energy metabolism. Conversely, constitutively active SRF-VP16 induced formation of mitochondrial networks and rescued huntingtin (HTT)-impaired mitochondrial dynamics. Finally, SRF and actin dynamics are connected via the actin severing protein cofilin and its slingshot phosphatase to modulate neuronal mitochondrial dynamics. In summary, our data suggest that the SRF-cofilin-actin signaling axis modulates neuronal mitochondrial function.</jats:p>
AU  - Beck,H
AU  - Flynn,K
AU  - Lindenberg,KS
AU  - Schwarz,H
AU  - Bradke,F
AU  - Di,Giovanni S
AU  - Knöll,B
DO  - 10.1073/pnas.1208141109
PY  - 2012///
SN  - 0027-8424
TI  - Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.1208141109
VL  - 109
ER  -
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