Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters

• Verfasst von: Breckwoldt, Michael O. [VerfasserIn]
• Verfasst von: Armoundas, Antonis A. [VerfasserIn]
• Verfasst von: Aon, Miguel A. [VerfasserIn]
• Verfasst von: Bendszus, Martin [VerfasserIn]
• Verfasst von: O’Rourke, Brian [VerfasserIn]
• Verfasst von: Schwarzländer, Markus [VerfasserIn]
• Verfasst von: Dick, Tobias P. [VerfasserIn]
• Verfasst von: Kurz, Felix T. [VerfasserIn]
• Titel: Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters
• Verf.angabe: Michael O. Breckwoldt, Antonis A. Armoundas, Miguel A. Aon, Martin Bendszus, Brian O’Rourke, Markus Schwarzländer, Tobias P. Dick, Felix T. Kurz
• E-Jahr: 2016
• Jahr: 22 March 2016
• Umfang: 12 S.
• Fussnoten: Gesehen am 19.05.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2016
• Band/Heft Quelle: 6(2016) Artikel-Nummer 23251, 12 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/srep23251
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698522290

Abstract

Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 ± 4.8 μm2). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations.