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

Michael O. Breckwoldt, Franz M.J. Pfister, Peter M. Bradley, Petar Marinković, Philip R. Williams, Monika S. Brill, Barbara Plomer, Anja Schmalz, Daret K. St Clair, Ronald Naumann, Oliver Griesbeck, Markus Schwarzländer, Leanne Godinho, Florence M. Bareyre, Tobias P. Dick, Martin Kerschensteiner, Thomas Misgeld

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish
Pages (from-to)555-560
Number of pages6
JournalNature medicine
Volume20
Issue number5
DOIs
StatePublished - Apr 28 2014

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