title: Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo.
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.
authors.affiliation: 1] Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany. [2] Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany. [3].
authors.forename: Michael O
authors.initials: MO
authors.lastname: Breckwoldt
authors.affiliation: 1] Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany. [2] Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Franz M J
authors.initials: FM
authors.lastname: Pfister
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bradley
authors.affiliation: Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany.
authors.forename: Petar
authors.initials: P
authors.lastname: Marinković
authors.affiliation: Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Williams
authors.affiliation: Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany.
authors.forename: Monika S
authors.initials: MS
authors.lastname: Brill
authors.affiliation: Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Plomer
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmalz
authors.affiliation: Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
authors.affiliation: Transgenic Core Facility, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.affiliation: Max-Planck Institute of Neurobiology, Martinsried, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Griesbeck
authors.affiliation: Institute of Crop Science and Resource Conservation (INRES), University of Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarzländer
authors.affiliation: Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany.
authors.forename: Leanne
authors.initials: L
authors.lastname: Godinho
authors.affiliation: 1] Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Bareyre
authors.affiliation: Division of Redox Regulation, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tobias P
authors.initials: TP
authors.lastname: Dick
authors.affiliation: 1] Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. [3].
authors.forename: Martin
authors.initials: M
authors.lastname: Kerschensteiner
authors.affiliation: 1] Institute for Neuronal Cell Biology, Technical University Munich, Munich, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. [3] German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. [4] Center for Integrated Protein Sciences (CIPS), Munich, Germany. [5].
authors.forename: Thomas
authors.initials: T
authors.lastname: Misgeld
mesh_terms: D000818:Animals; D019771:Axotomy; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism; D003952:Diagnostic Imaging; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium
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