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Updated: Jun 30, 2026

Live Imaging of the Mitochondrial Glutathione Redox State in Primary Neurons using a Ratiometric Indicator
Published on: October 20, 2021
A dominant role of GTRAP3-18 in neuronal glutathione synthesis
Masahiko Watabe1, Koji Aoyama, Toshio Nakaki
1Department of Pharmacology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
Abstract:
Glutathione is an essential reductant which protects cells and is reduced in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Neurons rely mainly on extracellular cysteine for glutathione synthesis and a cysteine transporter termed excitatory amino acid carrier 1 (EAAC1). However, the mechanisms underlying neuronal cysteine uptake have remained elusive. Herein, we show glutamate transport-associated protein for EAAC1 (GTRAP3-18) to interact with EAAC1 at the plasma membrane and thereby regulate neuronal glutathione levels. Glutathione increased in the mouse brain as well as in primary cultured neurons, when the GTRAP3-18 protein level was decreased by genetic manipulations, whereas glutathione decreased when GTRAP3-18 was increased. Furthermore, glutathione contents that had been increased, by a translocator and activator of EAAC1, were suppressed by increased cell surface GTRAP3-18 protein. Our results demonstrate GTRAP3-18 to dominantly and negatively determine the intracellular glutathione contents in neurons.
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