Ca(2+) handling in isolated brain mitochondria and cultured neurons derived from the YAC128 mouse model of Huntington's disease
dc.contributor.author | Pellman, Jessica J. | |
dc.contributor.author | Hamilton, James | |
dc.contributor.author | Brustovetsky, Tatiana | |
dc.contributor.author | Brustovetsky, Nickolay | |
dc.contributor.department | Department of Pharmacology and Toxicology, IU School of Medicine | en_US |
dc.date.accessioned | 2017-06-05T20:21:30Z | |
dc.date.available | 2017-06-05T20:21:30Z | |
dc.date.issued | 2015-08 | |
dc.description.abstract | We investigated Ca(2+) handling in isolated brain synaptic and non-synaptic mitochondria and in cultured striatal neurons from the YAC128 mouse model of Huntington's disease. Both synaptic and non-synaptic mitochondria from 2- and 12-month-old YAC128 mice had larger Ca(2+) uptake capacity than mitochondria from YAC18 and wild-type FVB/NJ mice. Synaptic mitochondria from 12-month-old YAC128 mice had further augmented Ca(2+) capacity compared with mitochondria from 2-month-old YAC128 mice and age-matched YAC18 and FVB/NJ mice. This increase in Ca(2+) uptake capacity correlated with an increase in the amount of mutant huntingtin protein (mHtt) associated with mitochondria from 12-month-old YAC128 mice. We speculate that this may happen because of mHtt-mediated sequestration of free fatty acids thereby increasing resistance of mitochondria to Ca(2+)-induced damage. In experiments with striatal neurons from YAC128 and FVB/NJ mice, brief exposure to 25 or 100 μM glutamate produced transient elevations in cytosolic Ca(2+) followed by recovery to near resting levels. Following recovery of cytosolic Ca(2+), mitochondrial depolarization with FCCP produced comparable elevations in cytosolic Ca(2+), suggesting similar Ca(2+) release and, consequently, Ca(2+) loads in neuronal mitochondria from YAC128 and FVB/NJ mice. Together, our data argue against a detrimental effect of mHtt on Ca(2+) handling in brain mitochondria of YAC128 mice. We demonstrate that mutant huntingtin (mHtt) binds to brain synaptic and nonsynaptic mitochondria and the amount of mitochondria-bound mHtt correlates with increased mitochondrial Ca(2+) uptake capacity. We propose that this may happen due to mHtt-mediated sequestration of free fatty acids thereby increasing resistance of mitochondria to Ca(2+)-induced damage. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Pellman, J. J., Hamilton, J., Brustovetsky, T., & Brustovetsky, N. (2015). Ca2+ Handling in Isolated Brain Mitochondria and Cultured Neurons Derived from the YAC128 Mouse Model of Huntington’s Disease. Journal of Neurochemistry, 134(4), 652–667. http://doi.org/10.1111/jnc.13165 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/12851 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1111/jnc.13165 | en_US |
dc.relation.journal | Journal of Neurochemistry | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Huntington’s disease | en_US |
dc.subject | Striatum | en_US |
dc.subject | Mitochondria | en_US |
dc.subject | Neuron | en_US |
dc.subject | Calcium | en_US |
dc.subject | Permeability transition pore | en_US |
dc.title | Ca(2+) handling in isolated brain mitochondria and cultured neurons derived from the YAC128 mouse model of Huntington's disease | en_US |
dc.type | Article | en_US |