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Originally published In Press as doi:10.1074/jbc.M609635200 on January 23, 2007

J. Biol. Chem., Vol. 282, Issue 11, 8228-8236, March 16, 2007
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Mitochondrial Genome Integrity Mutations Uncouple the Yeast Saccharomyces cerevisiae ATP Synthase*Formula

Yamin Wang, Usha Singh, and David M. Mueller1

From the Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois 60064

The mitochondrial ATP synthase is a molecular motor, which couples the flow of protons with phosphorylation of ADP. Rotation of the central stalk within the core of ATP synthase effects conformational changes in the active sites driving the synthesis of ATP. Mitochondrial genome integrity (mgi) mutations have been previously identified in the {alpha}-, beta-, and {gamma}-subunits of ATP synthase in yeast Kluyveromyces lactis and trypanosome Trypanosoma brucei. These mutations reverse the lethality of the loss of mitochondrial DNA in petite negative strains. Introduction of the homologous mutations in Saccharomyces cerevisiae results in yeast strains that lose mitochondrial DNA at a high rate and accompanied decreases in the coupling of the ATP synthase. The structure of yeast F1-ATPase reveals that the mgi residues cluster around the {gamma}-subunit and selectively around the collar region of F1. These results indicate that residues within the mgi complementation group are necessary for efficient coupling of ATP synthase, possibly acting as a support to fix the axis of rotation of the central stalk.


Received for publication, October 12, 2006 , and in revised form, January 4, 2007.

* This work was supported by National Institutes of Health Grants R01-GM067091 and R01-GM066223 (to D. M. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1–S2 and Movie 1.

1 To whom correspondence should be addressed: 3333 Greenbay Rd., North Chicago, IL. Tel.: 847-578-8606; Fax: 847-578-3240; E-mail: David.Mueller{at}RosalindFranklin.edu.


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This article has been cited by other articles:


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H. Z. Mao, C. G. Abraham, A. M. Krishnakumar, and J. Weber
A Functionally Important Hydrogen-bonding Network at the {beta}DP/{alpha}DP Interface of ATP Synthase
J. Biol. Chem., September 5, 2008; 283(36): 24781 - 24788.
[Abstract] [Full Text] [PDF]




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