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, 20 (5), 555-60

Multiparametric Optical Analysis of Mitochondrial Redox Signals During Neuronal Physiology and Pathology in Vivo

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Multiparametric Optical Analysis of Mitochondrial Redox Signals During Neuronal Physiology and Pathology in Vivo

Michael O Breckwoldt et al. Nat Med.

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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References

    1. J Exp Med. 2000 Oct 2;192(7):1001-14 - PubMed
    1. J Biol Chem. 2004 May 21;279(21):22284-93 - PubMed
    1. Nat Methods. 2008 Sep;5(9):805-11 - PubMed
    1. EMBO J. 2013 Jul 3;32(13):1927-40 - PubMed
    1. J Neurosci. 1998 Jan 15;18(2):687-97 - PubMed

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