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2 Publications visible to you, out of a total of 2
Targeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions

Abstract (Expand)

Abstract Inflammation in the central nervous system can impair the function of neuronal mitochondria and contributes to axon degeneration in the common neuroinflammatory disease multiple sclerosis (MS). …le sclerosis (MS). Here we combine cell-type-specific mitochondrial proteomics with in vivo biosensor imaging to dissect how inflammation alters the molecular composition and functional capacity of neuronal mitochondria. We show that neuroinflammatory lesions in the mouse spinal cord cause widespread and persisting axonal ATP deficiency, which precedes mitochondrial oxidation and calcium overload. This axonal energy deficiency is associated with impaired electron transport chain function, but also an upstream imbalance of tricarboxylic acid (TCA) cycle enzymes, with several, including key rate-limiting, enzymes being depleted in neuronal mitochondria in experimental models and in MS lesions. Notably, viral overexpression of individual TCA enzymes can ameliorate the axonal energy deficits in neuroinflammatory lesions, suggesting that TCA cycle dysfunction in MS may be amendable to therapy.

Authors: Yi-Heng Tai, Daniel Engels, Giuseppe Locatelli, Ioanna Emmanouilidis, Caroline Fecher, Delphine Theodorou, Stephan A. Müller, Simon Licht-Mayer, Mario Kreutzfeldt, Ingrid Wagner, Natalia Prudente de Mello, Sofia-Natsouko Gkotzamani, Laura Trovò, Arek Kendirli, Almir Aljović, Michael O. Breckwoldt, Ronald Naumann, Florence M. Bareyre, Fabiana Perocchi, Don Mahad, Doron Merkler, Stefan F. Lichtenthaler, Martin Kerschensteiner, Thomas Misgeld

Date Published: 10th Jul 2023

Publication Type: Journal Article

Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation

Abstract

Not specified

Authors: Mehrnoosh Jafari, Adrian-Minh Schumacher, Nicolas Snaidero, Emily M. Ullrich Gavilanes, Tradite Neziraj, Virág Kocsis-Jutka, Daniel Engels, Tanja Jürgens, Ingrid Wagner, Juan Daniel Flórez Weidinger, Stephanie S. Schmidt, Eduardo Beltrán, Nellwyn Hagan, Lisa Woodworth, Dimitry Ofengeim, Joseph Gans, Fred Wolf, Mario Kreutzfeldt, Ruben Portugues, Doron Merkler, Thomas Misgeld, Martin Kerschensteiner

Date Published: 25th Jan 2021

Publication Type: Journal Article

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