Decreased mitochondrial biogenesis in temperature-sensitive cell division cycle mutants of Saccharomyces cerevisiae

Genta, Hugo Dante; Mónaco, Marı́a E.; Aon, Miguel A.

doi:10.1007/bf00294693

Cited by 7 publications

(6 citation statements)

References 8 publications

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“…The results shown in Figures 4 and 5 and unpublished data support the latter idea, and further suggest that there is a threshold in the length of G1 below which the kinase expresses to higher levels. Furthermore, several cdc mutants showed a strong carbon and energetic uncoupling as well as decreased mitochondrial biogenesis during arrest of cell proliferation at the restrictive temperature Genta et al, 1995;Mónaco et al, 1995). It was suggested that the latter effects could be linked to carbon catabolite repression .…”

Section: Discussionmentioning

confidence: 99%

“…A likely interpretation of the latter results was that growth on gluconeogenic carbon sources, that occurs at slower rates than on glucose, might require a dose of the p34 CDC28 kinase low enough to be accomplished by the cdc28 mutant under these conditions . It has been suggested that the strong carbon and energetic uncoupling exhibited by several cdc mutants during arrest of cell proliferation at the restrictive temperature, could be linked to carbon catabolite repression Genta et al, 1995;Monaco et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Several reports point to the fact that the expression of CDC28 would be roughly constant throughout the cell division cycle of yeast (Johnston, 1992;Mendenhall, 1987). On the other hand, the cell cycle behavior of cdc mutants and the temperature-induced proliferation arrest suggest a relationship to their catabolite repression properties Cortassa, 1995, 1997;Genta et al, 1995;Mónaco et al, 1995). Thus, it is worth asking about the extent at which the CDC28 gene is expressed during growth on various carbon sources and under different genetic backgrounds with respect to catabolite (de)repression properties.…”

Section: Introductionmentioning

confidence: 99%

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Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose‐limited chemostat cultures

Aon

Cortassa

1998

Biotechnol. Bioeng.

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In glucose-limited continuous cultures, a Crabtree positive yeast such as Saccharomyces cerevisiae displays respiratory metabolism at low dilution rates (D) and respiro-fermentative metabolism at high D. We have studied the onset of ethanol production and cell cycle behavior in glucose-limited chemostat cultures of the wild type S. cerevisiae strain CEN.PK122 (WT) and isogenic mutants, snf1 (cat1) and snf4 (cat3) defective in proteins involved in catabolite derepression and the mutant in glucose repression mig1 (cat4). The triggering of fermentative metabolism was dependent upon catabolite repression properties of yeast and was coincident with a significant decrease of G1 length. WT cells of the strain CEN.PK122 displayed respiratory metabolism up to a D of 0.2 h-1 and exhibited longer G1 lengths than the snf1 and snf4 mutants that started fermenting after a D of 0.1 and 0.15 h-1, respectively. The catabolite derepression mutant snf4 showed a significant decrease in the duration of G1 with respect to the WT. An increase of 300% to 400% in the expression of CDC28 (CDC28-lacZ) with a noticeable shortening in G1 to values lower than approximately 150 min, was detected in the transformed wild type CEN.SC13-9B in glucose-limited chemostat cultures. The expression of CDC28-lacZ was analyzed in the wild type and isogenic mutant strains growing at maximal rate on glucose or in the presence of ethanol or glycerol. Two- to three-fold lower expression of the CDC28-lacZ fusion gene was detected in the snf1 or snf4 disruptants with respect to the WT and mig1 strains in the presence of all carbon sources. This effect was further shown to be growth rate-dependent exhibiting apparently, a threshold effect in the expression of the fusion gene with respect to the length of G1, similar to that shown in chemostat cultures. At the onset of fermentation, the control of the glycolytic flux was highly distributed between the uptake, hexokinase, and phosphofructokinase steps. Particularly interesting was the fact that the snf1 mutant exhibited the lowest fluxes of ethanol production, the highest of respiration and correspondingly, the branch to the tricarboxylic acid cycle was significantly rate-controling of glycolysis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose‐limited chemostat cultures

Aon

Cortassa

1998

Biotechnol. Bioeng.

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“…Several of the original CDC alleles, which cause cell cycle defects when grown at the non-permissive temperature, were later discovered to also result in reduced carbon metabolism and lower ATP production [61] . Conversely, mutations in cell cycle genes, such as the cyclin-dependent kinase CDC28 were found to also affect mitochondria biogenesis [62] . This metabolism-cell cycle connection has been studied in detail in budding yeast.…”

Section: The Mitochondria Meets the Cell Cyclementioning

confidence: 99%

Genomic heterogeneity meets cellular energetics: crosstalk between the mitochondria and the cell cycle

Herrera¹,

Azzam²,

Berger³

et al. 2018

JCMT

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Changes in cellular energetics and genomic instability are two characteristics of cancers that have been studied independently. Evidence of cross-talk between mitochondria function and nuclear function has started to emerge, suggesting that these pathways can influence one another. Here we review recent evidence that links the mitochondria and the cell cycle. This evidence indicates bidirectional cross-talk where mitochondria function can regulate the cell cycle and induce genomic instability, and conversely, the cell cycle machinery regulates mitochondria function. Implications for this cross-talk in the development of cancer are discussed.

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“…[20] This argument is further supported by studies involving yeast cell division cycle (cdc) mutants. Interestingly, cdc28 and cdc35 show decreased mitochondrial biogenesis[21] and cdc5 and cdc27 show defects in mitochondrial segregation[22] as well as in nuclear division. Other examples include cdc8 and cdc21 mutants defective in nuclear DNA replication during the S phase of the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

p53 regulates mtDNA copy number and mitocheckpoint pathway

Kulawiec¹,

Vanniarajan²,

Singh³

2009

J Carcinog

120

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Background:We previously hypothesized a role for mitochondria damage checkpoint (mito-checkpoint) in maintaining the mitochondrial integrity of cells. Consistent with this hypothesis, defects in mitochondria have been demonstrated to cause genetic and epigenetic changes in the nuclear DNA, resistance to cell-death and tumorigenesis. In this paper, we describe that defects in mitochondria arising from the inhibition of mitochondrial oxidative phosphorylation (mtOXPHOS) induce cell cycle arrest, a response similar to the DNA damage checkpoint response.Materials and Methods:Primary mouse embryonic fibroblasts obtained from p53 wild-type and p53-deficient mouse embryos (p53 -/-) were treated with inhibitors of electron transport chain and cell cycle analysis, ROS production, mitochondrial content analysis and immunoblotting was performed. The expression of p53R2 was also measured by real time quantitative PCR.Results:We determined that, while p53 +/+ cells arrest in the cell cycle, p53 -/- cells continued to divide after exposure to mitochondrial inhibitors, showing that p53 plays an important role in the S-phase delay in the cell cycle. p53 is translocated to mitochondria after mtOXPHOS inhibition. Our study also revealed that p53-dependent induction of reactive oxygen species acts as a major signal triggering a mito-checkpoint response. Furthermore our study revealed that loss of p53 results in down regulation of p53R2 that contributes to depletion of mtDNA in primary MEF cells.Conclusions:Our study suggests that p53 1) functions as mito-checkpoint protein and 2) regulates mtDNA copy number and mitochondrial biogenesis. We describe a conceptual organization of the mito-checkpoint pathway in which identified roles of p53 in mitochondria are incorporated.

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Decreased mitochondrial biogenesis in temperature-sensitive cell division cycle mutants of Saccharomyces cerevisiae

Cited by 7 publications

References 8 publications

Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose‐limited chemostat cultures

Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose‐limited chemostat cultures

Genomic heterogeneity meets cellular energetics: crosstalk between the mitochondria and the cell cycle

p53 regulates mtDNA copy number and mitocheckpoint pathway

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