The Two Rotor Components of Yeast Mitochondrial ATP Synthase Are Mechanically Coupled by Subunit Delta

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Oct 29

PMID 14581615

Citations 23

Authors

Stephane Duvezin-Caubet

Matthieu Caron

Marie-France Giraud

Jean Velours

Jean-Paul di Rago

Affiliations

Soon will be listed here.

Abstract

The mitochondrial ATP synthase is made of a membrane-integrated F0 component that forms a proton-permeable pore through the inner membrane and a globular peripheral F1 domain where ATP is synthesized. The catalytic mechanism is thought to involve the rotation of a 10-12 c subunit ring in the F0 together with the gamma subunit of F1. An important and not yet resolved question is to define precisely how the gamma subunit is connected with the c-ring. In this study, using a doxycycline-regulatable expression system, we provide direct evidence that the rest of the enzyme can assemble without the delta subunit of F1, and we show that delta-less mitochondria are uncoupled because of an F0-mediated proton leak. Based on these observations, and taking into account high-resolution structural models, we propose that subunit delta plays a key role in the mechanical coupling of the c-ring to subunit gamma.

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References

Schulenberg B, Aggeler R, Murray J, Capaldi R . The gammaepsilon-c subunit interface in the ATP synthase of Escherichia coli. cross-linking of the epsilon subunit to the c subunit ring does not impair enzyme function, that of gamma to c subunits leads to uncoupling. J Biol Chem. 1999; 274(48):34233-7. DOI: 10.1074/jbc.274.48.34233. View

Gari E, Piedrafita L, Aldea M, Herrero E . A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae. Yeast. 1997; 13(9):837-48. DOI: 10.1002/(SICI)1097-0061(199707)13:9<837::AID-YEA145>3.0.CO;2-T. View

Sambongi Y, Iko Y, Tanabe M, Omote H, Ueda I, Yanagida T . Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Science. 1999; 286(5445):1722-4. DOI: 10.1126/science.286.5445.1722. View

Xiao Y, Metzl M, Mueller D . Partial uncoupling of the mitochondrial membrane by a heterozygous null mutation in the gene encoding the gamma- or delta-subunit of the yeast mitochondrial ATPase. J Biol Chem. 2000; 275(10):6963-8. DOI: 10.1074/jbc.275.10.6963. View

Panke O, Gumbiowski K, Junge W, Engelbrecht S . F-ATPase: specific observation of the rotating c subunit oligomer of EF(o)EF(1). FEBS Lett. 2000; 472(1):34-8. DOI: 10.1016/s0014-5793(00)01436-8. View

Fillingame R . Getting to the bottom of the F1-ATPase. Nat Struct Biol. 2000; 7(11):1002-4. DOI: 10.1038/80902. View

Gibbons C, Montgomery M, Leslie A, Walker J . The structure of the central stalk in bovine F(1)-ATPase at 2.4 A resolution. Nat Struct Biol. 2000; 7(11):1055-61. DOI: 10.1038/80981. View

Stock D, Gibbons C, Arechaga I, Leslie A, Walker J . The rotary mechanism of ATP synthase. Curr Opin Struct Biol. 2000; 10(6):672-9. DOI: 10.1016/s0959-440x(00)00147-0. View

Tsunoda S, Aggeler R, Yoshida M, Capaldi R . Rotation of the c subunit oligomer in fully functional F1Fo ATP synthase. Proc Natl Acad Sci U S A. 2001; 98(3):898-902. PMC: 14681. DOI: 10.1073/pnas.98.3.898. View

10.

Vaillier J, Benabdelhak H, Velours J, SLONIMSKI P, di Rago J . Identification of a nuclear gene (FMC1) required for the assembly/stability of yeast mitochondrial F(1)-ATPase in heat stress conditions. J Biol Chem. 2000; 276(9):6789-96. DOI: 10.1074/jbc.M009557200. View

11.

BOYER P . The ATP synthase--a splendid molecular machine. Annu Rev Biochem. 1997; 66:717-49. DOI: 10.1146/annurev.biochem.66.1.717. View

12.

Noji H, Yasuda R, Kinosita Jr K, Yoshida M . Direct observation of the rotation of epsilon subunit in F1-ATPase. J Biol Chem. 1998; 273(31):19375-7. DOI: 10.1074/jbc.273.31.19375. View

13.

Lai-Zhang J, Xiao Y, Mueller D . Epistatic interactions of deletion mutants in the genes encoding the F1-ATPase in yeast Saccharomyces cerevisiae. EMBO J. 1999; 18(1):58-64. PMC: 1171102. DOI: 10.1093/emboj/18.1.58. View

14.

Chen X, Clark-Walker G . The petite mutation in yeasts: 50 years on. Int Rev Cytol. 1999; 194:197-238. DOI: 10.1016/s0074-7696(08)62397-9. View

15.

Cruciat C, Hell K, Folsch H, Neupert W, Stuart R . Bcs1p, an AAA-family member, is a chaperone for the assembly of the cytochrome bc(1) complex. EMBO J. 1999; 18(19):5226-33. PMC: 1171593. DOI: 10.1093/emboj/18.19.5226. View

16.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

17.

Velours J, Arselin G . The Saccharomyces cerevisiae ATP synthase. J Bioenerg Biomembr. 2002; 32(4):383-90. DOI: 10.1023/a:1005580020547. View

18.

Mueller D . Partial assembly of the yeast mitochondrial ATP synthase. J Bioenerg Biomembr. 2002; 32(4):391-400. DOI: 10.1023/a:1005532104617. View

19.

Suzuki T, Ueno H, Mitome N, Suzuki J, Yoshida M . F(0) of ATP synthase is a rotary proton channel. Obligatory coupling of proton translocation with rotation of c-subunit ring. J Biol Chem. 2002; 277(15):13281-5. DOI: 10.1074/jbc.M111210200. View

20.

Lefebvre-Legendre L, Balguerie A, Duvezin-Caubet S, Giraud M, Slonimski P, di Rago J . F1-catalysed ATP hydrolysis is required for mitochondrial biogenesis in Saccharomyces cerevisiae growing under conditions where it cannot respire. Mol Microbiol. 2003; 47(5):1329-39. DOI: 10.1046/j.1365-2958.2003.03371.x. View