The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects glutathione redox homeostasis

Abstract

Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is synthesized de novo solely in the cytosol and must subsequently be transported to other cellular compartments. The mechanisms of glutathione transport into and out of organelles remain largely unclear. We show that budding yeast Opt2, a close homolog of the plasma membrane glutathione transporter Opt1, localizes to peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox homeostasis. Furthermore, ∆opt2 strains display synthetic lethality with deletions of genes central to iron homeostasis that require mitochondrial glutathione redox homeostasis. Our results shed new light on the importance of peroxisomes in cellular glutathione homeostasis.

Metabolic excretion associated with nutrient-growth dysregulation promotes the rapid evolution of an overt metabolic defect

“…Furthermore, our data suggest that compared to GSH, GS-X might be preferentially exported ( Fig 2C), consistent with cells purging unwanted GS-X. Our findings are consistent with previous observations that yeast upregulated glutathione transporters such as Gex1 and excreted GSH and GS-X 38 in response to cadmium-induced redox stress, and that Opt1, an oligopeptide transporter shown to export GSH 39 , was upregulated in response to different environmental stressors 40,41 .…”

Temporal profiling of redox-dependent heterogeneity in single cells

“…S1), such that we could sort yeast subpopulations according to their redox status. This approach was also applied to organelle-specific redox sensors, such as the mitochondrial Grx1-roGFP2-Su9 22 and the peroxisomal Grx1-roGFP2-SKL 25 , revealing a similar redox sensitivity ( Fig. S1).…”

Hyperoxidation of mitochondrial peroxiredoxin limits H 2 O 2 ‐induced cell death in yeast

“…Compartment-specific NADPH-independent systems to regulate E GSH E GSH is robustly maintained in most investigated compartments (Meyer et al, 2007;Kojer et al, 2012;Morgan et al, 2013;Elbaz-Alon et al, 2014). In the cytosol and the matrix, NADPH-dependent glutathione reductase provides the major mechanism of E GSH maintenance.…”