Failure to Assemble the α3 β3 Subcomplex of the ATP Synthase Leads to Accumulation of the α and β Subunits within Inclusion Bodies and the Loss of Mitochondrial Cristae in Saccharomyces cerevisiae

Lefebvre-Legendre, Linnka; Salin, Bénédicte; Schaeffer, Jacques; Brèthes, Daniel; Dautant, Alain; Ackerman, Sharon H.; Rago, J.P. Di

doi:10.1074/jbc.m410789200

Cited by 63 publications

(64 citation statements)

References 53 publications

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“…31,32 As already stated, Dfmc1 cells grown at nonpermissive temperature are known to accumulate a-F1 and b-F1 aggregates in the mitochondrial matrix. 22 A tempting hypothesis would, therefore, be that the autophagic process depicted here could result from a similar signalling initiated by these matricial aggregates. However, Dfmc1 cells grown under aerobic conditions at 371C (Figure 2d) show typical mitochondria harbouring such matricial aggregates (dashed arrows), and yet, autophagy was never detected either by EM (Figure 2d) or with the ALP test (Figure 3, white bar).…”

Section: Resultsmentioning

confidence: 94%

“…processed to remove the amino-terminal targeting peptide). [20][21][22] These mutants hence lack functional ATP synthase. Such a defect becomes a major issue in respiration-deficient cells, where the maintenance of an electrical potential across the mitochondrial inner membrane (DC) is no longer provided by the respiratory chain, but should be generated by the reverse functioning of the mitochondrial ATP synthase and the mitochondrial ATP/ADP carrier (ANC): normally in nonrespiring cells, the ANC imports ATP and exports ADP, and the F1-catalysed ATP hydrolysis is coupled to proton extrusion toward the mitochondrial inter-membrane space, thus maintaining a weaker DC.…”

Section: Resultsmentioning

confidence: 99%

“…However, in Dfmc1 cells grown under such conditions, F1 sector was not correctly assembled into a functional Fo-F1 ATPase, since DC collapse prevents Atp1p import into mitochondria; non imported Atp1p might still be trapped into aggregates. [20][21][22] Such an enrichment of proteins in clusters might provide a clue for a more efficient degradation of Atp1p compared to Por1p. It is nonetheless noteworthy that in both cases, this degradation was largely prevented in the macroautophagy-deficient double mutant Dfmc1 Datg5.…”

Section: Resultsmentioning

confidence: 99%

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Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

et al. 2005

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Autophagy, a highly regulated programme found in almost all eukaryotes, is mainly viewed as a catabolic process that degrades nonessential cellular components into molecular building blocks, subsequently available for biosynthesis at a lesser expense than de novo synthesis. Autophagy is largely known to be regulated by nutritional conditions. Here we show that, in yeast cells grown under nonstarving conditions, autophagy can be induced by mitochondrial dysfunction. Electron micrographs and biochemical studies show that an autophagic activity can result from impairing the mitochondrial electrochemical transmembrane potential. Furthermore, mitochondrial damage-induced autophagy results in the preferential degradation of impaired mitochondria (mitophagy), before leading to cell death. Mitophagy appears to rely on classical macroautophagy machinery while being independent of cellular ATP collapse. These results suggest that in this case, autophagy can be envisioned either as a process of mitochondrial quality control, or as an ultimate cellular response triggered when cells are overwhelmed with damaged mitochondria.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

et al. 2005

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“…Like complex III and IV mutants, the ATP2-RNAi knock-down mutant was an obligate photoautotroph. In addition, as observed in yeast mutants [55,56] lack of ATP synthase in Chlamydomonas also affected the morphology of mitochondria, which were deprived of cristae. In contrast, the loss of Asa7 subunit had no impact on cell bioenergetics or mitochondrial structures [31].…”

Section: Mutants Affected In Complex Vmentioning

confidence: 75%

Respiratory-deficient mutants of the unicellular green alga Chlamydomonas: A review

et al. 2014

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Genetic manipulation of the unicellular green alga Chlamydomonas reinhardtii is straightforward. Nuclear genes can be interrupted by insertional mutagenesis or targeted by RNA interference whereas random or site-directed mutagenesis allows the introduction of mutations in the mitochondrial genome. This, combined with a screen that easily allows discriminating respiratorydeficient mutants, makes Chlamydomonas a model system of choice to study mitochondria biology in photosynthetic organisms. Since the first description of Chlamydomonas respiratory-deficient mutants in 1977 by random mutagenesis, many other mutants affected in mitochondrial components have been characterized. These respiratory-deficient mutants increased our knowledge on function and assembly of the respiratory enzyme complexes. More recently some of these mutants allowed the study of mitochondrial gene expression processes poorly understood in Chlamydomonas. In this review, we update the data concerning the respiratory components with a special focus on the assembly factors identified on other organisms. In addition, we make an inventory of different mitochondrial respiratory mutants that are inactivated either on mitochondrial or nuclear genes. Opposed Reviewers:Claire Remacle -Génétique des microorganismes -Institut de Botanique B22 Boulevard du Rectorat, 27 -Université de Liège-B-4000 Liège, Belgique Tel +32 4 3663812 -Fax +32 4 3663840 e-mail: c.remacle@ulg.ac.be First, we wish to thank the two anonymous reviewers for their constructive comments. We found their suggestions very helpful to improve the quality of our manuscript. We have addressed all the points they raised and have modified the text accordingly. A detailed response to reviewers' comments is included below.We believe we have addressed all referees' comments and we hope this revised version is now suitable for publication in Biochimie.We are looking forward to hearing from you, With best regards, Cover LetterResponse to reviewers The text has been modified in order to give more background details on the methodology used to create and screen respiratory mutants in Chlamydomonas. The main modifications correspond to: Paragraph 2.3: -p8. A figure (Fig. 4) has been added in order to provide more information on dark-dier/slow growth screens for different classes of mutant.-p9. The mitochondrial transformation method used in Chlamydomonas has been detailed.Paragraph 2.4: -p10. The TTC-based screen has been explained.Finally, all along the text the methods used to create nuclear and mitochondrial mutants has been indicated. Also, the text could benefit from being proof-read by a native English speaker as the grammar is a little awkward in places. I highlight a couple of points below, but there are a number of other places where the English could be improved for clarity.The text has been proof-read by a good English speaker as requested and the text has been modified according to the comments.Minor points:1. Abstract, line 1: "the genetics" have been replaced by "genetic manipu...

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“…The ␥-less subcomplexes would be expected to be at least partially assembled in vivo to hydrolyze ATP, which allows the survival of o cells. It is possible that the protein-dense environment and/or the presence of F 1 -specific chaperones (e.g., Atp11, Atp12, and Fmc1) (39)(40)(41)(42)(43)(44) in the mitochondrial matrix may stabilize the ␥-less subcomplexes in vivo.…”

Section: Discussionmentioning

confidence: 99%

Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F ₁ -ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor

Clark-Walker

Wang

et al. 2013

Eukaryot Cell

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F 1 -ATPase is a rotary molecular machine with a subunit stoichiometry of ␣ 3 ␤ 3 ␥ 1 ␦ 1 1 . It has a robust ATP-hydrolyzing activity due to effective cooperativity between the three catalytic sites. It is believed that the central ␥ rotor dictates the sequential conformational changes to the catalytic sites in the ␣ 3 ␤ 3 core to achieve cooperativity. However, recent studies of the thermophilic Bacillus PS3 F 1 -ATPase have suggested that the ␣ 3 ␤ 3 core can intrinsically undergo unidirectional cooperative catalysis (T. Uchihashi et al., Science 333:755-758, 2011). The mechanism of this ␥-independent ATP-hydrolyzing mode is unclear. Here, a unique genetic screen allowed us to identify specific mutations in the ␣ and ␤ subunits that stimulate ATP hydrolysis by the mitochondrial F 1 -ATPase in the absence of ␥. We found that the F446I mutation in the ␣ subunit and G419D mutation in the ␤ subunit suppress cell death by the loss of mitochondrial DNA ( o ) in a Kluyveromyces lactis mutant lacking ␥. In organello ATPase assays showed that the mutant but not the wild-type ␥-less F 1 complexes retained 21.7 to 44.6% of the native F 1 -ATPase activity. The ␥-less F 1 subcomplex was assembled but was structurally and functionally labile in vitro. Phe446 in the ␣ subunit and Gly419 in the ␤ subunit are located on the N-terminal edge of the DELSEED loops in both subunits. Mutations in these two sites likely enhance the transmission of catalytically required conformational changes to an adjacent ␣ or ␤ subunit, thereby allowing robust ATP hydrolysis and cell survival under o conditions. This work may help our understanding of the structural elements required for ATP hydrolysis by the ␣ 3 ␤ 3 subcomplex.

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Failure to Assemble the α3 β3 Subcomplex of the ATP Synthase Leads to Accumulation of the α and β Subunits within Inclusion Bodies and the Loss of Mitochondrial Cristae in Saccharomyces cerevisiae

Cited by 63 publications

References 53 publications

Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

Respiratory-deficient mutants of the unicellular green alga Chlamydomonas: A review

Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F ₁ -ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor

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Failure to Assemble the α3 β3 Subcomplex of the ATP Synthase Leads to Accumulation of the α and β Subunits within Inclusion Bodies and the Loss of Mitochondrial Cristae in Saccharomyces cerevisiae

Cited by 63 publications

References 53 publications

Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast

Respiratory-deficient mutants of the unicellular green alga Chlamydomonas: A review

Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F 1 -ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor

Contact Info

Product

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Mutations on the N-Terminal Edge of the DELSEED Loop in either the α or β Subunit of the Mitochondrial F ₁ -ATPase Enhance ATP Hydrolysis in the Absence of the Central γ Rotor