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Molecular and Cellular Biology, May 2000, p. 3677-3684, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of the Mitochondrial Hsp70s, Ssc1 and Ssq1, in the Maturation of Yfh1

Cindy Voisine,1 Brenda Schilke,1 Maikke Ohlson,1 Helmut Beinert,2 Jaroslaw Marszalek,1,3 and Elizabeth A. Craig1,*

Department of Biomolecular Chemistry1 and Institute for Enzyme Research and the Department of Biochemistry,2 University of Wisconsin, Madison, Wisconsin 53706, and Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, 80-822 Gdansk, Poland3

Received 20 October 1999/Returned for modification 7 December 1999/Accepted 28 February 2000

The mitochondrial matrix of the yeast Saccharomyces cerevisiae contains two molecular chaperones of the Hsp70 class, Ssc1 and Ssq1. We report that Ssc1 and Ssq1 play sequential roles in the import and maturation of the yeast frataxin homologue (Yfh1). In vitro, radiolabeled Yfh1 was not imported into ssc1-3 mutant mitochondria, remaining in a protease-sensitive precursor form. As reported earlier, the Yfh1 intermediate form was only slowly processed to the mature form in Delta ssq1 mitochondria (S. A. B. Knight, N. B. V. Sepuri, D. Pain, and A. Dancis, J. Biol. Chem. 273:18389-18393, 1998). However, the intermediate form in both wild-type and Delta ssq1 mitochondria was entirely within the inner membrane, as it was resistant to digestion with protease after disruption of the outer membrane. Therefore, we conclude that Ssc1, which is present in mitochondria in approximately a 1,000-fold excess over Ssq1, is required for Yfh1 import into the matrix, while Ssq1 is necessary for the efficient processing of the intermediate to the mature form in isolated mitochondria. However, the steady-state level of mature Yfh1 in Delta ssq1 mitochondria is approximately 75% of that found in wild-type mitochondria, indicating that this retardation in processing does not dramatically affect cellular concentrations. Therefore, Ssq1 likely has roles in addition to facilitating the processing of Yfh1. Twofold overexpression of Ssc1 partially suppresses the cold-sensitive growth phenotype of Delta ssq1 cells, as well as the accumulation of mitochondrial iron and the defects in Fe/S enzyme activities normally found in Delta ssq1 mitochondria. Delta ssq1 mitochondria containing twofold-more Ssc1 efficiently converted the intermediate form of Yfh1 to the mature form. This correlation between the observed processing defect and suppression of in vivo phenotypes suggests that Ssc1 is able to carry out the functions of Ssq1, but only when present in approximately a 2,000-fold excess over normal levels of Ssq1.

* Corresponding author. Mailing address: Department of Biomolecular Chemistry, University of Wisconsin, 1300 University Ave., Madison, WI 53706. Phone: (608) 262-1358. Fax: (608) 262-5253. E-mail: ecraig{at}facstaff.wisc.edu.

Molecular and Cellular Biology, May 2000, p. 3677-3684, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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