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

Details

Serval ID
serval:BIB_1A35D62A2AC4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Glutathione S-Transferase Regulates Mitochondrial Populations in Axons through Increased Glutathione Oxidation.
Journal
Neuron
Author(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
Publication state
Published
Issued date
03/07/2019
Peer-reviewed
Oui
Volume
103
Number
1
Pages
52-65.e6
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
25/05/2019 13:24
Last modification date
25/10/2019 14:39
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