Glutathione S-Transferase Regulates Mitochondrial Populations in Axons through Increased Glutathione Oxidation.

Détails

ID Serval
serval:BIB_1A35D62A2AC4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glutathione S-Transferase Regulates Mitochondrial Populations in Axons through Increased Glutathione Oxidation.
Périodique
Neuron
Auteur⸱e⸱s
Smith G.A., Lin T.H., Sheehan A.E., Van der Goes van Naters W., Neukomm L.J., Graves H.K., Bis-Brewer D.M., Züchner S., Freeman M.R.
ISSN
1097-4199 (Electronic)
ISSN-L
0896-6273
Statut éditorial
Publié
Date de publication
03/07/2019
Peer-reviewed
Oui
Volume
103
Numéro
1
Pages
52-65.e6
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Mitochondria are essential in long axons to provide metabolic support and sustain neuron integrity. A healthy mitochondrial pool is maintained by biogenesis, transport, mitophagy, fission, and fusion, but how these events are regulated in axons is not well defined. Here, we show that the Drosophila glutathione S-transferase (GST) Gfzf prevents mitochondrial hyperfusion in axons. Gfzf loss altered redox balance between glutathione (GSH) and oxidized glutathione (GSSG) and initiated mitochondrial fusion through the coordinated action of Mfn and Opa1. Gfzf functioned epistatically with the thioredoxin peroxidase Jafrac1 and the thioredoxin reductase 1 TrxR-1 to regulate mitochondrial dynamics. Altering GSH:GSSG ratios in mouse primary neurons in vitro also induced hyperfusion. Mitochondrial changes caused deficits in trafficking, the metabolome, and neuronal physiology. Changes in GSH and oxidative state are associated with neurodegenerative diseases like Alzheimer's. Our demonstration that GSTs are key in vivo regulators of axonal mitochondrial length and number provides a potential mechanistic link.
Mots-clé
Animals, Axons/physiology, Axons/ultrastructure, Carrier Proteins/physiology, Drosophila, Drosophila Proteins/genetics, Drosophila Proteins/physiology, Female, Glutathione/metabolism, Membrane Proteins/genetics, Membrane Proteins/physiology, Mice, Mice, Inbred C57BL, Mitochondria/physiology, Neurons/metabolism, Oxidation-Reduction, Peroxidases/genetics, Peroxidases/physiology, Pregnancy, Primary Cell Culture, Thioredoxin Reductase 1/genetics, Thioredoxin Reductase 1/physiology, Gfzf, axons, glutathione, glutathione S-transferases, marf, mitochondria, mitofusin, neurons, redox
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/05/2019 13:24
Dernière modification de la notice
25/10/2019 14:39
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