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Originally published as MBC in Press, 10.1091/mbc.E06-09-0801 on November 29, 2006

Vol. 18, Issue 2, 617-626, February 2007

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The Metalloprotease Encoded by ATP23 Has a Dual Function in Processing and Assembly of Subunit 6 of Mitochondrial ATPase

Xiaomei Zeng*, Walter Neupert{dagger}, and Alexander Tzagoloff*

*Department of Biological Sciences, Columbia University, New York, NY 10027; and {dagger}Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, München 81377, Germany

Submitted September 19, 2006; Revised November 17, 2006; Accepted November 21, 2006
Monitoring Editor: Thomas Fox

In the present study we have identified a new metalloprotease encoded by the nuclear ATP23 gene of Saccharomyces cerevisiae that is essential for expression of mitochondrial ATPase (F1-FO complex). Mutations in ATP23 cause the accumulation of the precursor form of subunit 6 and prevent assembly of FO. Atp23p is associated with the mitochondrial inner membrane and is conserved from yeast to humans. A mutant harboring proteolytically inactive Atp23p accumulates the subunit 6 precursor but is nonetheless able to assemble a functional ATPase complex. These results indicate that removal of the subunit 6 presequence is not an essential event for ATPase biogenesis and that Atp23p, in addition to its processing activity, must provide another important function in FO assembly. The product of the yeast ATP10 gene was previously shown to interact with subunit 6 and to be required for its association with the subunit 9 ring. In this study one extra copy of ATP23 was found to be an effective suppressor of an atp10 null mutant, suggesting an overlap in the functions of Atp23p and Atp10p. Atp23p may, therefore, also be a chaperone, which in conjunction with Atp10p mediates the association of subunit 6 with the subunit 9 ring.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-09-0801) on November 29, 2006.

1 While these studies were in progress, we learned that Osman et al. (2007) obtained similar data.

Address correspondence to: Alexander Tzagoloff (spud{at}cubpet.bio.columbia.edu)

Abbreviations used: {rho}o mutant, respiratory-deficient mutant lacking mitochondrial DNA; {rho} mutant, respiratory-deficient mutant with a partially deleted mitochondrial genome; pet mutant, respiratory-deficient mutant of yeast with a mutation in a nuclear gene; DOC, potassium deoxycholate; PMSF, phenylmethylsulfonyl fluoride; SMP, submitochondrial particles.




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