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Eukaryotic Cell, December 2008, p. 2160-2167, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00106-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Thiol-Independent Action of Mitochondrial Thioredoxin To Support the Urea Cycle of Arginine Biosynthesis in Schizosaccharomyces pombe{triangledown}

Ji-Yoon Song, Kyoung-Dong Kim, and Jung-Hye Roe*

Laboratory of Molecular Microbiology, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea

Received 24 March 2008/ Accepted 30 September 2008

Thioredoxins usually perform a role as a thiol-disulfide oxidoreductase using their active-site cysteines. The fission yeast Schizosaccharomyces pombe contains two thioredoxins: Trx1 for general stress protection and Trx2 for mitochondrial functions. The {Delta}trx2 mutant grows as well as the wild type on complex media containing glucose. However, on nonfermentable carbon source such as glycerol, the mutant did not grow, indicating a defect in mitochondrial function. The mutant also exhibited auxotrophy for arginine and cysteine on minimal medium. In order to find the reason for the unexpected arginine auxotrophy, we searched for multicopy suppressors and found that the arg3+ gene encoding ornithine carbamoyltransferase (OCTase) in the urea cycle of the arginine biosynthetic pathway rescued the arginine auxotrophy. The levels of arg3+ transcript, Arg3 protein, and OCTase activity were all decreased in {Delta}trx2. Through immunocoprecipitation, we observed a direct interaction between Trx2 and Arg3 in cell extracts. The mutant forms of Trx2 lacking either one or both of the active site cysteines through substitution to serines also rescued the arginine auxotrophy and restored the decreased OCTase activity. They also rescued the growth defect of {Delta}trx2 on glycerol medium. This contrasts with the thiol-dependent action of overproduced Trx2 in complementing glutathione reductase. Therefore, Trx2 serves multiple functions in mitochondria, protecting mitochondrial components against thiol-oxidative damage as a thiol-disulfide oxidoreductase, and supporting urea cycle and respiration in mitochondria in a manner independent of active site thiols.

* Corresponding author. Mailing address: School of Biological Sciences, Seoul National University, 56-1 Shillim-dong, Kwanak-gu, Seoul 151-742, Korea. Phone: 82-2-880-6706. Fax: 82-2-888-4911. E-mail: jhroe{at}snu.ac.kr

{triangledown} Published ahead of print on 10 October 2008.

Eukaryotic Cell, December 2008, p. 2160-2167, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00106-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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