Selection of the nuclear gene for the mitochondrial adenine nucleotide translocator by genetic complementation of the op1 mutation in yeast.

O’Malley, Karen L.; Pratt, Patricia L.; Robertson, John M.; Lilly, Mary A.; Douglas, Michael G.

doi:10.1016/s0021-9258(19)68151-2

Cited by 68 publications

(4 citation statements)

References 47 publications

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“…The yeast Saccharomyces cerevisiae ScAnc2p affords a very convenient tool because its gene can be easily mutagenized. Three nuclear genes encode ScAncp, but only ScANC2 is required for growth on nonfermentable carbon sources. − A three-dimensional (3D) model of ScAnc2p in the CATR conformation was built from the BtAnc1p crystal structure because the amino acid sequences of both proteins are 47% identical. This allowed the rationalization of mutagenesis sites to unravel the nucleotide-binding site and pathway during nucleotide transport .…”

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confidence: 99%

Mitochondrial ADP/ATP Carrier: Preventing Conformational Changes by Point Mutations Inactivates Nucleotide Transport Activity

et al. 2012

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The mitochondrial ADP/ATP carrier (Ancp) is a paradigm of the mitochondrial carrier family (MCF); its members allow metabolic fluxes between mitochondria and the cytosol. The members of the MCF share numerous structural and functional characteristics. Ancp is very specifically inhibited by two classes of compounds, which stabilize the carrier in two different conformations involved in nucleotide transport. Resolution of the atomic structure of the bovine Ancp, in complex with one of its specific inhibitors, is that of the carrier open toward the intermembrane space. To gain insights into the interconversion from one conformation to the other, we introduced point mutations in the yeast carrier at positions Cys73 in the first matrix loop and Tyr97 and Gly298 in transmembrane helices 2 and 6. We demonstrate in this paper that they impair stabilization of the carrier in one conformation or the other, resulting in an almost complete inactivation of nucleotide transport in both cases. The results are discussed on the basis of the atomic structure of the conformation open to the cytosol. These mutant proteins could afford convenient tools for undertaking structural studies of both conformations of the yeast carrier.

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confidence: 99%

Mitochondrial ADP/ATP Carrier: Preventing Conformational Changes by Point Mutations Inactivates Nucleotide Transport Activity

et al. 2012

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“…Analyses of mitochondria isolated from the op1 mutant cells, including the response of parameters of respiration to bongkrekic acid and atractyloside, specific inhibitors of mitochondrial ADP/ATP transport, indicated that the mutation may affect the ADP/ATP translocator of inner mitochondrial membrane [23,24], a protein whose existence in mitochondria was suggested earlier, when transport of ATP and ADP was initially investigated using rat liver mitochondria [25,26]. Genetic screening of the yeast genomic library later resulted in identification of the first gene encoding for mitochondrial carrier protein-AAC1 [27], (at the same time when the sequence of bovine ADP/ATP carrier was determined by protein sequencing [28]) and the second gene encoding for a major yeast isoform of the carrier-AAC2 [29]. The op1 mutation was shown to be a single amino acid substitution in Aac2p (Arg96His) [30].…”

Section: Adp/atp Carriermentioning

confidence: 99%

Learning from Yeast about Mitochondrial Carriers

et al. 2021

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Mitochondria are organelles that play an important role in both energetic and synthetic metabolism of eukaryotic cells. The flow of metabolites between the cytosol and mitochondrial matrix is controlled by a set of highly selective carrier proteins localised in the inner mitochondrial membrane. As defects in the transport of these molecules may affect cell metabolism, mutations in genes encoding for mitochondrial carriers are involved in numerous human diseases. Yeast Saccharomyces cerevisiae is a traditional model organism with unprecedented impact on our understanding of many fundamental processes in eukaryotic cells. As such, the yeast is also exceptionally well suited for investigation of mitochondrial carriers. This article reviews the advantages of using yeast to study mitochondrial carriers with the focus on addressing the involvement of these carriers in human diseases.

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“…Moreover, the up-regulation of the PET9 (2.0Â) gene, coding for the major ATP/ADP carrier that exchanges the mitochondrial ATP by the cytosolic ADP, was also observed. 28 There is an indication in the literature that the PET9 gene is essential for growth on nonfermentable carbon sources, such as ethanol and glycerol. 29 In addition, the up-regulation of the RGI1 (2.0Â) and RGI2 (4.0Â) genes, coding for proteins of unknown functions associated with respiratory growth, was also observed.…”

Section: Mitochondrial Functions Are Affected By Mg II Even In Anaero...mentioning

confidence: 99%

Magnesium ions in yeast: setting free the metabolism from glucose catabolite repression

et al. 2016

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In a recent work we showed that magnesium (Mg) plays an important role in industrial ethanol production, overcoming the negative effect of the excess of minerals, particularly copper, present in sugarcane juice, with a consequent increase in ethanol yield. This cation has been reported to be involved in several steps of yeast metabolism, acting mainly as a co-factor of several enzymes of fermentation metabolism and protecting yeast cells from stressful conditions. However, despite many physiological investigations, its effect in the molecular mechanisms that control such metabolic activities remains unclear and to date no information concerning its influence on gene expression has been provided. The present work took advantage of the DNA microarray technology to analyse the global gene expression in yeast cells upon fermentation in Mg-supplemented medium. The results of the fermentation parameters confirmed the previous report on the increase in ethanol yield by Mg. Moreover, the gene expression data revealed an unexpected set of up-regulated genes currently assigned as being negatively-regulated by glucose, which belong to respiratory and energy metabolism, the stress response and the glyoxalate cycle. On the other hand, genes involved in ribosome biogenesis were down-regulated. Computational analysis provided evidence for a regulatory network commanded by key transcriptional factors that may be responsible for the biological action of Mg in yeast cells. In this scenario, Mg seems to act by reprogramming the yeast metabolism by releasing many genes from glucose catabolite repression with positive consequences for ethanol production and maintenance of cell viability.

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Selection of the nuclear gene for the mitochondrial adenine nucleotide translocator by genetic complementation of the op1 mutation in yeast.

Cited by 68 publications

References 47 publications

Mitochondrial ADP/ATP Carrier: Preventing Conformational Changes by Point Mutations Inactivates Nucleotide Transport Activity

Mitochondrial ADP/ATP Carrier: Preventing Conformational Changes by Point Mutations Inactivates Nucleotide Transport Activity

Learning from Yeast about Mitochondrial Carriers

Magnesium ions in yeast: setting free the metabolism from glucose catabolite repression

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