Burtscher 2015 Mitochondrion: Difference between revisions
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* 2015-11-16: MitoFit in the brain. Β» [[MitoFit news]] |
Revision as of 11:46, 7 December 2015
Burtscher J, Zangrandi L, Schwarzer C, Gnaiger E (2015) Differences in mitochondrial function in homogenated samples from healthy and epileptic specific brain tissues revealed by high-resolution respirometry. Mitochondrion 25:104-12. |
Burtscher J, Zangrandi L, Schwarzer C, Gnaiger E (2015) Mitochondrion
Abstract: Mitochondrial dysfunction and oxidative stress are strongly implicated in neurodegenerative diseases and epilepsy. Strikingly, neurodegenerative diseases show regional specificity in vulnerability and follow distinct patterns of neuronal loss. A challenge is to understand, why mitochondria fail in particular brain regions under specific pathological conditions. A potential explanation could be provided by regional or cellular specificity of mitochondrial function.
We applied high-resolution respirometry to analyze the integrated Complex I- and II (CI and CII)-linked respiration, the activity of Complex IV, and the combined CI&II-linked oxidative phosphorylation (OXPHOS)- and electron-transfer system (ETS)-capacity in microsamples obtained from distinct regions of the mouse brain. We compared different approaches to assess mitochondrial density and suggest flux control ratios as a valid method to normalize respiration to mitochondrial density.
This approach revealed significant differences of CI- and CII-linked OXPHOS capacity and coupling control between motor cortex, striatum, hippocampus and pons of naΓ―ve mice. CI-linked respiration was highest in motor cortex, while CII-linked respiration predominated in the striatum. To investigate if this method could also determine differences in normal and disease states within the same brain region, we compared hippocampal homogenates in a chronic epilepsy model. Three weeks after stereotaxic injection of kainate, there was a down-regulation of CI- and upregulation of CII-linked respiration in the resulting epileptic ipsilateral hippocampus compared to the contralateral one.
In summary, respirometric OXPHOS analysis provides a very sensitive diagnostic approach using small amounts of distinct brain tissues. In a single assay, information is obtained on numerous OXPHOS parameters as indicators of tissue-specific mitochondrial performance. β’ Keywords: Neurodegeneration, Epilepsy, Mitochondria, Brain regions, Respirometry
β’ O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck OROBOROS
Labels: MiParea: Respiration, Instruments;methods, mt-Biogenesis;mt-density, Pharmacology;toxicology
Pathology: Neurodegenerative
Stress:Mitochondrial disease
Organism: Mouse
Tissue;cell: Nervous system
Preparation: Permeabilized tissue, Homogenate
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
PBI - Shredder
MitoFit news 2015#17
- 2015-11-16: MitoFit in the brain. Β» MitoFit news