Suppression of ρ
0 lethality by mitochondrial ATP synthase F1 mutations in Kluyveromyces lactis occurs in the absence of F0

Chen, X. J.; Hansbro, Philip M.; Clark-Walker, G. D.

doi:10.1007/s004380050836

Cited by 18 publications

(8 citation statements)

References 53 publications

(45 reference statements)

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“…After incubation for 48 h at 28°C the surviving cells on the margin between growth and non-growth were substreaked, followed by incubation for 12 days before photography mtDNA by EB (data not shown) is consistent with this interpretation. Further supporting evidence comes from studies showing that q o lethality of K. lactis cells can be suppressed by speci®c F 1 mutations, in the absence of the six major F o proteins, namely Atp4p, 5p, 6p, 7p, 8p and 9p (Chen et al 1998). The combined evidence excludes any possibility that the q o -lethality suppressor function of F 1 operates by activating proton back pumping or blocking proton¯ux through a residual F o .…”

Section: Discussionmentioning

confidence: 93%

“…The resulting plasmids, pScATP2/159, pScATP2/430 and pScATP2/588, were linearised by cleavage with StuI in the URA3 gene and targeted onto the ura3 locus of the atp2-disrupted mutant CS114 to produce CS162, CS163 and CS164. To introduce the K. lactis atp1-2 allele (formerly mgi2-2) into S. cerevisiae, the plasmid pURA-Klatp1.2 was constructed by cloning of a 2.8-kb KpnI-BamHI fragment containing the Klatp1-2 allele from pCXJ3-mgi2.2 (Chen et al 1998) into pUC-URA3/4. pURA-Klatp1.2 was linearised by digestion with StuI in the URA3 gene and integrated into the ura3 locus of CS113 to produce CS187.…”

Section: Gene Disruption and Strain Constructionmentioning

confidence: 99%

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α and β subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae

Chen¹,

Clark-Walker²

1999

Mol Gen Genet

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Although Saccharomyces cerevisiae can form petite mutants with deletions in mitochondrial DNA (mtDNA) (rho-) and can survive complete loss of the organellar genome (rho(o)), the genetic factor(s) that permit(s) survival of rho- and rho(o) mutants remain(s) unknown. In this report we show that a function associated with the F1-ATPase, which is distinct from its role in energy transduction, is required for the petite-positive phenotype of S. cerevisiae. Inactivation of either the alpha or beta subunit, but not the gamma, delta, or epsilon subunit of F1, renders cells petite-negative. The F1 complex, or a subcomplex composed of the alpha and beta subunits only, is essential for survival of rho(o) cells and those impaired in electron transport. The activity of F1 that suppresses rho(o) lethality is independent of the membrane Fo complex, but is associated with an intrinsic ATPase activity. A further demonstration of the ability of F1 subunits to suppress rho(o) lethality has been achieved by simultaneous expression of S. cerevisiae F1 alpha and gamma subunit genes in Kluyveromyces lactis - which allows this petite-negative yeast to survive the loss of its mtDNA. Consequently, ATP1 and ATP2, in addition to the previously identified AAC2, YME1 and PEL1/PGS1 genes, are required for establishment of rho- or rho(o) mutations in S. cerevisiae.

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Section: Discussionmentioning

confidence: 93%

Section: Gene Disruption and Strain Constructionmentioning

confidence: 99%

α and β subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae

Chen¹,

Clark-Walker²

1999

Mol Gen Genet

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“…64, 2000 MAINTENANCE OF THE MITOCHONDRIAL GENOME 305 tion of an altered F 1 complex that was able to prevent the leakage of protons, allowing the survival of petites (37). This hypothesis has been rather complicated by recent data which show that cells lacking the mitochondrial ATP9 gene or disrupted for three nuclear genes (ATP4, ATP5, ATP7) encoding F 0 subunits are viable (39). The obvious conclusion is that lack of F 0 per se is not responsible for petite death.…”

Section: Petite Positivity Versus Petite Negativity: Atpase In the Fomentioning

confidence: 99%

“…The obvious conclusion is that lack of F 0 per se is not responsible for petite death. As emphasized by the authors, it remains to be determined if loss of ATP6 and/or ATP8 leads to cell death (39). If not, the mitochondrial component for the vital function of mtDNA will have to be identified, along with the role played by F 1 .…”

Section: Petite Positivity Versus Petite Negativity: Atpase In the Fomentioning

confidence: 99%

Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast

Contamine

Picard

2000

Microbiol Mol Biol Rev

264

209

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SUMMARY Instability of the mitochondrial genome (mtDNA) is a general problem from yeasts to humans. However, its genetic control is not well documented except in the yeast Saccharomyces cerevisiae. From the discovery, 50 years ago, of the petite mutants by Ephrussi and his coworkers, it has been shown that more than 100 nuclear genes directly or indirectly influence the fate of the rho+ mtDNA. It is not surprising that mutations in genes involved in mtDNA metabolism (replication, repair, and recombination) can cause a complete loss of mtDNA (rho0 petites) and/or lead to truncated forms (rho−) of this genome. However, most loss-of-function mutations which increase yeast mtDNA instability act indirectly: they lie in genes controlling functions as diverse as mitochondrial translation, ATP synthase, iron homeostasis, fatty acid metabolism, mitochondrial morphology, and so on. In a few cases it has been shown that gene overexpression increases the levels of petite mutants. Mutations in other genes are lethal in the absence of a functional mtDNA and thus convert this petite-positive yeast into a petite-negative form: petite cells cannot be recovered in these genetic contexts. Most of the data are explained if one assumes that the maintenance of the rho+ genome depends on a centromere-like structure dispensable for the maintenance of rho− mtDNA and/or the function of mitochondrially encoded ATP synthase subunits, especially ATP6. In fact, the real challenge for the next 50 years will be to assemble the pieces of this puzzle by using yeast and to use complementary models, especially in strict aerobes.

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“…14 The F 1 portion of the ATP synthase plays a major role in generating the essential ∆Ψ mito of ρmitochondria through a poorly understood electrogenic circuit thought to require the F 1 sector's ability to hydrolyze ATP [14,18,20,[85][86][87]. The F 1 sector performs this role even in the absence of a functional F O sector of the ATP synthase [88], which is partially encoded by the mitochondrial genome. Interestingly, the atp2∆ mutant, which lacks F 1 activity, was also rescued following mtDNA loss by attenuation of PKA (Fig.…”

Section: Overexpression Of Pde2p Can Suppress the Petite-negative Phementioning

confidence: 99%

Reduced Glucose Sensation Can Increase the Fitness ofSaccharomyces cerevisiaeLacking Mitochondrial DNA

Akdoğan

Tardu

Garipler

et al. 2015

Preprint

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Damage to the mitochondrial genome (mtDNA) can lead to diseases for which there are no clearly effective treatments. Since mitochondrial function and biogenesis are controlled by the nutrient environment of the cell, it is possible that perturbation of conserved, nutrient-sensing pathways may successfully treat mitochondrial disease. We found that restricting glucose or otherwise reducing the activity of the protein kinase A (PKA) pathway can lead to improved fitness for Saccharomyces cerevisiae cells lacking mtDNA, and the transcriptional response to mtDNA loss is reduced in cells with diminished PKA activity. We have excluded many pathways and proteins from being individually responsible for the benefits provided by PKA inhibition to cells lacking mtDNA, and we found that robust import of mitochondrial polytopic membrane proteins may be required in order for cells without mtDNA to receive the full benefits of PKA reduction. Finally, we have discovered that the transcription of genes involved in arginine biosynthesis and aromatic amino acid catabolism is altered after mtDNA damage. Our results highlight the potential importance of nutrient detection and availability on the outcome of mitochondrial dysfunction.we asked whether any individual isoform of PKA might play a specific role in determining the outcome of mtDNA loss. Tpk1p, Tpk2p, and Tpk3p are the three PKA isoforms encoded by S. cerevisiae [28]. All three proteins act redundantly to allow cell proliferation, since tpk1∆ tpk2∆ tpk3∆ cells are normally inviable [32]. However, it is likely that each PKA isoform controls divergent cellular processes by phosphorylating its own specific set of target proteins [28,33]. We found that single deletion of Tpk3p increased the proliferation of ρcells (Fig. 1B). Deletion of the other PKA catalytic subunits, either singly or in combination, did not benefit cells lacking mtDNA.Interestingly, deletion of either Tpk1p or, more prominently, Tpk2p decreased the proliferation rate of tpk3∆ ρcells, potentially suggesting a complex relationship between the PKA isoforms in which one PKA isoform might act upstream of another isoform in order to enact a signaling outcome. "PKA activity is promoted by Gpr1p, a G-protein coupled receptor, and Gpa2p, an associated G-protein α subunit [28,34]. We asked whether deletion of Gpr1p or Gpa2p would improve the fitness of ρcells. Both gpr1∆ ρand gpa2∆ ρcells proliferated more rapidly than isogenic WT ρcells (Fig. 1C), further supporting a role for PKA activity in decreasing the fitness of cells lacking mtDNA. ρcells lacking Tpk3p proliferate more slowly than gpr1∆ ρcells and gpa2∆ ρcells. This finding may suggest complex control of PKA isoforms by Gpr1p and Gpa2p beyond what is accessible by experiments using single and double Tpk deletion mutants. Alternatively this result may support an additional function for Gpr1p/Gpa2p outside of its role within the PKA pathway that is detrimental to proliferation of ρcells. Glucose restriction benefits cells lacking mitochondrial DNA" Since a reductio...

show abstract

Suppression of ρ 0 lethality by mitochondrial ATP synthase F1 mutations in Kluyveromyces lactis occurs in the absence of F0

Cited by 18 publications

References 53 publications

α and β subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae

α and β subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae

Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast

Reduced Glucose Sensation Can Increase the Fitness ofSaccharomyces cerevisiaeLacking Mitochondrial DNA

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