A conserved mitochondrial ATP-binding cassette transporter exports glutathione polysulfide for cytosolic metal cofactor assembly

Schaedler, Theresia A, Thornton, Jeremy D, Kruse, Inga, Schwarzländer, Markus, Meyer, Andreas J, van Veen, Hendrik W and Balk, Janneke (2014) A conserved mitochondrial ATP-binding cassette transporter exports glutathione polysulfide for cytosolic metal cofactor assembly. Journal of Biological Chemistry, 289. pp. 23264-23274. ISSN 0021-9258

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Abstract

An ATP-binding cassette (ABC) transporter located in the inner mitochondrial membrane is involved in iron-sulfur cluster and molybdenum cofactor assembly in the cytosol, but the transported substrate is unknown. ATM3 (ABCB25) from Arabidopsis thaliana and its functional orthologue Atm1 from Saccharomyces cerevisiae were expressed in Lactococcus lactis, and studied in inside-out membrane vesicles and in purified form. Both proteins selectively transported glutathione disulfide (GSSG) but not reduced glutathione (GSH) in agreement with a 3-fold stimulation of ATPase activity by GSSG. By contrast, Fe2+ alone or in combination with glutathione did not stimulate ATPase activity. Arabidopsis atm3 mutants were hypersensitive to an inhibitor of glutathione biosynthesis, and accumulated GSSG in the mitochondria. The growth phenotype of atm3-1 was strongly enhanced by depletion of the mitochondria-localized, GSH-dependent persulfide oxygenase ETHE1, suggesting that the physiological substrate of ATM3 contains persulfide in addition to glutathione. Consistent with this idea, a transportomics approach using mass spectrometry showed that glutathione trisulfide (GS-S-SG) was transported by Atm1. We propose that mitochondria export glutathione polysulfide, containing glutathione and persulfide, for iron-sulfur cluster assembly in the cytosol.

Item Type: Article
Additional Information: Free via Open Access
Uncontrolled Keywords: abc transporter,arabidopsis,iron-sulfur protein,mitochondria,yeast,glutathione,transportomics
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 19 Aug 2014 09:04
Last Modified: 21 Apr 2020 23:22
URI: https://ueaeprints.uea.ac.uk/id/eprint/49931
DOI: 10.1074/jbc.M114.553438

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