Bovine Coupling Factor 6, with Just 14.5% Shared Identity, Replaces Subunit h in the Yeast ATP Synthase

Institut de Biochimie et Génétique Cellulaires du CNRS, Université Victor Ségalen, Bordeaux 2, 1 rue Camille Saint Saëns, 33077 Bordeaux, cedex France.
Journal of Biological Chemistry (Impact Factor: 4.57). 04/2001; 276(11):8602-7. DOI: 10.1074/jbc.M008123200
Source: PubMed


The mammalian mitochondrial ATP synthase is composed of at least 16 polypeptides. With the exception of coupling factor F6, there are likely yeast homologs for each of these polypeptides. There are no obvious yeast homologs of F6, as predicted from primary sequence comparison of the putative peptides encoded by the open reading frames in the yeast genome.
In this manuscript, we demonstrate that expression of bovine F6 complements a null mutant in ATP14 gene in yeast Saccharomyces cerevisiae. Subunit h of the yeast ATP synthase is encoded by ATP14 and is just 14.5% identical to bovine F6. Expression of bovine F6 in an atp14 null mutant strain recovers oxidative phosphorylation, and the ATP synthase is active, although functioning with
a lower efficiency than the wild type enzyme. Like subunith, bovine F6 is shown to interact mainly with subunit 4 (subunit b), a component of the second stalk of the enzyme. These data indicated the subunith is the yeast homolog of mammalian coupling factor F6.

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    • "The subunit h shares only 15% identity with the bovine coupling factor F 6 and is 16 residues longer than F 6 (Velours et al., 2001). Two helices linked by a proline rich loop are predicted at the N-terminal while the C-terminal part appeared as an unstructured tail in agreement with the bovine structures (Dickson et al., 2006; Rees et al., 2009). "
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    ABSTRACT: Mitochondrial F(1)F(o) ATP synthase is an enzymatic complex involved in the aerobic synthesis of ATP. It is well known that several enzymes are organized in supramolecular complexes in the inner mitochondrial membrane. The ATP synthase supramolecular assembly is mediated through two interfaces. One leads to dimer formation and the other to oligomer formation. In yeast, the presence of ATP synthase oligomers has been described as essential to the maintenance of the mitochondrial cristae ultrastructure. Indeed, the destabilization of the interactions between monomers was shown to alter the organization of the inner mitochondrial membrane, leading to the formation of onion-like structures similar to those observed in some mitochondrial pathologies. By using information obtained this decade (structure modeling, electron microscopy and cross-linking), this paper (i) reviews the actual state of the art and (ii) proposes a topological model of the transmembrane domains and interfaces of the ATP synthase's tetramer. This review also discusses the physiological role of this oligomerization process and its potential implications in mammal pathology. This article is part of a Directed Issue entitled: Bioenergetic Dysfunction, adaptation and therapy.
    The international journal of biochemistry & cell biology 06/2012; 45(1). DOI:10.1016/j.biocel.2012.05.017 · 4.05 Impact Factor
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    • "Mitochondrial F 1 F 0 ATP synthase was assayed in mitochondrial preparations as described [22]. Oligomycin at 6 μg/ml, an inhibitor of this enzyme [23], was used for background subtraction. Mitochondria were prepared as described [19]. "
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    ABSTRACT: Iron overload is involved in several pathological conditions, including Friedreich ataxia, a disease caused by decreased expression of the mitochondrial protein frataxin. In a previous study, we identified 14 proteins selectively oxidized in yeast cells lacking Yfh1, the yeast frataxin homolog. Most of these were magnesium-binding proteins. Decreased Mn-SOD activity, oxidative damage to CuZn-SOD, and increased levels of chelatable iron were also observed in this model. This study explores the relationship between low SOD activity, the presence of chelatable iron, and protein damage. We observed that addition of copper and manganese to the culture medium restored SOD activity and prevented both oxidative damage and inactivation of magnesium-binding proteins. This protection was compartment specific: recovery of mitochondrial enzymes required the addition of manganese, whereas cytosolic enzymes were recovered by adding copper. Copper treatment also decreased Deltayfh1 sensitivity to menadione. Finally, a Deltasod1 mutant showed high levels of chelatable iron and inactivation of magnesium-binding enzymes. These results suggest that reduced superoxide dismutase activity contributes to the toxic effects of iron overloading. This would also apply to pathologies involving iron accumulation.
    Free Radical Biology and Medicine 11/2009; 48(3):411-20. DOI:10.1016/j.freeradbiomed.2009.11.010 · 5.74 Impact Factor
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    • "In the light of the C-terminal localisation of yeast F 6 (subunit h) close to the membrane surface [51], it seemed more likely that F 6 assembled in the peripheral stalk would have an extended linear conformation oriented approximately along the long axis of the peripheral stalk, with the N-terminus nearer the top and the C-terminus pointing towards the membrane (Fig. 8) [51]. The sequences of bovine F 6 and its yeast homologue, subunit h, are 14.5% identical [56]. The yeast protein is 16 residues longer than the bovine protein. "
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    ABSTRACT: The peripheral stalk of F-ATPases is an essential component of these enzymes. It extends from the membrane distal point of the F1 catalytic domain along the surface of the F1 domain with subunit a in the membrane domain. Then, it reaches down some 45 A to the membrane surface, and traverses the membrane, where it is associated with the a-subunit. Its role is to act as a stator to hold the catalytic alpha3beta3 subcomplex and the a-subunit static relative to the rotary element of the enzyme, which consists of the c-ring in the membrane and the attached central stalk. The central stalk extends up about 45 A from the membrane surface and then penetrates into the alpha3beta3 subcomplex along its central axis. The mitochondrial peripheral stalk is an assembly of single copies of the oligomycin sensitivity conferral protein (the OSCP) and subunits b, d and F6. In the F-ATPase in Escherichia coli, its composition is simpler, and it consists of a single copy of the delta-subunit with two copies of subunit b. In some bacteria and in chloroplasts, the two copies of subunit b are replaced by single copies of the related proteins b and b' (known as subunits I and II in chloroplasts). As summarized in this review, considerable progress has been made towards establishing the structure and biophysical properties of the peripheral stalk in both the mitochondrial and bacterial enzymes. However, key issues are unresolved, and so our understanding of the role of the peripheral stalk and the mechanism of synthesis of ATP are incomplete.
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