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Updated: Jul 11, 2025

Ratiometric Biosensors that Measure Mitochondrial Redox State and ATP in Living Yeast Cells
Published on: July 22, 2013
Autoregulatory control of mitochondrial glutathione homeostasis
Yuyang Liu1, Shanshan Liu1, Anju Tomar2,3
1Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
Abstract:
Mitochondria must maintain adequate amounts of metabolites for protective and biosynthetic functions. However, how mitochondria sense the abundance of metabolites and regulate metabolic homeostasis is not well understood. In this work, we focused on glutathione (GSH), a critical redox metabolite in mitochondria, and identified a feedback mechanism that controls its abundance through the mitochondrial GSH transporter, SLC25A39. Under physiological conditions, SLC25A39 is rapidly degraded by mitochondrial protease AFG3L2. Depletion of GSH dissociates AFG3L2 from SLC25A39, causing a compensatory increase in mitochondrial GSH uptake. Genetic and proteomic analyses identified a putative iron-sulfur cluster in the matrix-facing loop of SLC25A39 as essential for this regulation, coupling mitochondrial iron homeostasis to GSH import. Altogether, our work revealed a paradigm for the autoregulatory control of metabolic homeostasis in organelles.
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