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Difference between revisions of "Burtscher 2015 Mitochondrion"

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|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.
|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.
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 (ET-pathway)-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 naïve 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.
This approach revealed significant differences of CI- and CII-linked OXPHOS capacity and coupling control between motor cortex, striatum, hippocampus and pons of naïve 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.
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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.
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.
|keywords=Neurodegeneration, Epilepsy, Mitochondria, Brain regions, Respirometry
|keywords=Neurodegeneration, Epilepsy, Mitochondria, Brain regions, Respirometry
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck OROBOROS
|editor=[[Gnaiger E]]
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck Oroboros
}}
}}
{{Labeling
{{Labeling
|area=Respiration, Instruments;methods, mt-Biogenesis;mt-density, Pharmacology;toxicology
|area=Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology
|diseases=Neurodegenerative
|organism=Mouse
|organism=Mouse
|tissues=Nervous system
|tissues=Nervous system
|preparations=Permeabilized tissue, Homogenate
|preparations=Permeabilized tissue, Homogenate
|injuries=Mitochondrial disease
|couplingstates=LEAK, OXPHOS, ET
|diseases=Neurodegenerative
|pathways=N, S, CIV, NS, ROX
|couplingstates=LEAK, OXPHOS, ETS
|substratestates=CI, CII, CIV, CI&II, ROX
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=PBI - Shredder, MitoFit news
|additional=PBI-Shredder
}}
}}
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== MitoFit news 2015#17 ==
== MitoFit news 2015#17 ==
* 2015-11-16: MitoFit in the brain. » [[MitoFit news]]
::::* 2015-11-16: MitoFit in the brain. » [[K-Regio_MitoFit#2015 |MitoFit news]]

Revision as of 15:06, 19 March 2019

Publications in the MiPMap
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.

» PMID: 26516105 Open Access

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 (ET-pathway)-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 naïve 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. Keywords: Neurodegeneration, Epilepsy, Mitochondria, Brain regions, Respirometry Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Permeabilized tissue, Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

PBI-Shredder 

MitoFit

MitoFit news 2015#17