title: Yeast mitochondrial glutathione is an essential antioxidant with mitochondrial thioredoxin providing a back-up system.
abstract: Glutathione is an abundant, low-molecular-weight tripeptide whose biological importance is dependent upon its redox-active free sulphydryl moiety. Its role as the main determinant of thiol-redox control has been challenged such that it has been proposed to play a crucial role in iron-sulphur clusters maturation, and only a minor role in thiol redox regulation, predominantly as a back-up system for the cytoplasmic thioredoxin system. Here, we have tested the importance of mitochondrial glutathione in thiol-redox regulation. Glutathione reductase (Glr1) is an oxidoreductase which converts oxidized glutathione to its reduced form. Yeast Glr1 localizes to both the cytosol and mitochondria and we have used a Glr1(M1L) mutant that is constitutively localized to the cytosol to test the requirement for mitochondrial Glr1. We show that the loss of mitochondrial Glr1 specifically accounts for oxidant sensitivity of a glr1 mutant. Loss of mitochondrial Glr1 does not influence iron-sulphur cluster maturation and we have used targeted roGFP2 fluorescent probes to show that oxidant sensitivity is linked to an altered redox environment. Our data indicate mitochondrial glutathione is crucial for mitochondrial thiol-redox regulation, and the mitochondrial thioredoxin system provides a back-up system, but cannot bear the redox load of the mitochondria on its own.
authors.affiliation: University of Manchester, Faculty of Life Sciences, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Irina
authors.initials: I
authors.lastname: Gostimskaya
authors.affiliation: University of Manchester, Faculty of Life Sciences, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Electronic address: chris.grant@manchester.ac.uk.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Grant
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D019803:Glutathione Disulfide; D005980:Glutathione Reductase / Q000235:genetics* / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007506:Iron-Sulfur Proteins; D013438:Sulfhydryl Compounds; D013879:Thioredoxins; D005980:Glutathione Reductase; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: Glutathione; Glutathione reductase; Mitochondria; Thioredoxin; Yeast