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  Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo

Breckwoldt, M., Pfister, F. M. J., Bradley, P. M., Marinkovic, P., Williams, P. R., Brilll, M. S., et al. (2014). Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Nature Medicine, 20(5), 555-560. doi:10.1038/nm.3520.

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 Creators:
Breckwoldt, Michael, Author
Pfister, Franz M. J., Author
Bradley, Peter M., Author
Marinkovic, Petar, Author
Williams, Philip R., Author
Brilll, Monika S., Author
Plomer, Barbara, Author
Schmalz, Anja, Author
St Clair, Daret K., Author
Naumann, Ronald, Author
Griesbeck, Oliver1, Author           
Schwarzlaender, Markus, Author
Godinho, Leanne, Author
Bareyre, Florence M., Author
Dick, Tobias P., Author
Kerschensteiner, Martin, Author
Misgeld, Thomas, Author
Affiliations:
1Research Group: Cellular Dynamics / Griesbeck, MPI of Neurobiology, Max Planck Society, ou_1113560              

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Free keywords: HYDROGEN-PEROXIDE; SUPEROXIDE FLASHES; PERMEABILITY TRANSITION; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; SPINAL-CORD; FLUORESCENT; REGENERATION; CALCIUM; CELLS
 Abstract: Mitochondrial redox signals have a central role in neuronal physiology and disease. Here we describe a new optical approach to measure fast redox signals with single-organelle resolution in living mice that express genetically encoded redox biosensors in their neuronal mitochondria. Moreover, we demonstrate how parallel measurements with several biosensors can integrate these redox signals into a comprehensive characterization of mitochondrial function. This approach revealed that axonal mitochondria undergo spontaneous 'contractions' that are accompanied by reversible redox changes. These contractions are amplified by neuronal activity and acute or chronic neuronal insults. Multiparametric imaging reveals that contractions constitute respiratory chain-dependent episodes of depolarization coinciding with matrix alkalinization, followed by uncoupling. In contrast, permanent mitochondrial damage after spinal cord injury depends on calcium influx and mitochondrial permeability transition. Thus, our approach allows us to identify heterogeneity among physiological and pathological redox signals, correlate such signals to functional and structural organelle dynamics and dissect the underlying mechanisms.

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Language(s): eng - English
 Dates: 2014-05
 Publication Status: Published in print
 Pages: 6
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000335710700029
DOI: 10.1038/nm.3520
 Degree: -

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Title: Nature Medicine
  Other : Nat. Med.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : Nature Pub. Co.
Pages: - Volume / Issue: 20 (5) Sequence Number: - Start / End Page: 555 - 560 Identifier: ISSN: 1078-8956
CoNE: https://pure.mpg.de/cone/journals/resource/954925606824