A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism

Michaeli, Simon; Fait, Aaron; Lagor, Kelly; Nunes‐Nesi, Adriano; Grillich, Nicole; Yellin, Ayelet; Bar, Dana; Khan, Munziba; Fernie, Alisdair R.; Turano, Frank J.; Fromm, Hillel

doi:10.1111/j.1365-313x.2011.04612.x

Cited by 181 publications

(129 citation statements)

References 51 publications

Supporting

Mentioning

124

Contrasting

Order By: Relevance

“…Here, we provide model-based evidence that GABA transport plays a functional role in augmenting the TCA cycle and maintaining of a normal metabolism (47). This claim is experimentally supported by demonstrating the existence of GABA flux into the mitochondrion in rat brain (52,53) as well as the recently demonstrated presence and (albeit relatively minor) functional role of a mitochondrial GABA permease (AtGABP) in both primary carbon metabolism and growth as well as its importance in ensuring proper GABA-mediated respiration in plants (47). It is important to mention that it is currently not experimentally possible to produce a mutant fully deficient in GABA uptake because we do not know the molecular nature of additional mitochondrial transporters.…”

Section: Discussionmentioning

confidence: 99%

“…Although the metabolic significance of GABA in plants and animals has not yet been fully understood (47), considerable advances in our understanding will probably be achieved by studying the dynamics of GABA distribution and transport. Here, we provide model-based evidence that GABA transport plays a functional role in augmenting the TCA cycle and maintaining of a normal metabolism (47).…”

Section: Discussionmentioning

confidence: 99%

“…Although this small discrepancy may still be indicative of phytanoyl-CoA acting as alternative substrate, closer inspection of RSS in Table 1 shows that for all metabolites, the model variant without phytanoyl-CoA results in pre- Finally, we investigate the extent to which our computational results depend on the inclusion of GABA transport in the model without phytanoyl-CoA. Although recent experimental evidence suggests that mitochondrial GABA permease plays a functional role in plants (47), its contribution to the maintenance of mitochondrial metabolism is not fully understood yet. Here we compare two variants of the model without phytanoylCoA: with and without GABA transport into the mitochondria (reaction 17).…”

Section: Modeling Of Mitochondrial Electron Transportmentioning

confidence: 99%

See 2 more Smart Citations

Model-based Confirmation of Alternative Substrates of Mitochondrial Electron Transport Chain

Kleeßen

Araújo

Fernie

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: There are alternative substrates to the mitochondrial respiration. Results: Data-driven model-based analysis renders predictions of alternative substrates to the mitochondrial respiration. Conclusion: Metabolomics data in conjunction with flux-based models can discriminate among hypotheses based on enzymology alone. Significance: This analysis provides a basic framework for in silico studies of alternative pathways in metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Modeling Of Mitochondrial Electron Transportmentioning

confidence: 99%

See 1 more Smart Citation

Model-based Confirmation of Alternative Substrates of Mitochondrial Electron Transport Chain

Kleeßen

Araújo

Fernie

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The GABA shunt activity could also provide a major supply of succinate to the TCA cycle during germination. This could be related to the established role of the GABA shunt in regulating the C/N ratio in conditions where the carbon supply is limited (123).…”

Section: Constitutive De Novo Synthesis Of Enzymes Involved In Energymentioning

confidence: 99%

Dynamic Proteomics Emphasizes the Importance of Selective mRNA Translation and Protein Turnover during Arabidopsis Seed Germination

Galland¹,

Huguet²,

Arc³

et al. 2014

Molecular & Cellular Proteomics

146

155

View full text Add to dashboard Cite

During seed germination, the transition from a quiescent metabolic state in a dry mature seed to a proliferative metabolic state in a vigorous seedling is crucial for plant propagation as well as for optimizing crop yield. This work provides a detailed description of the dynamics of protein synthesis during the time course of germination, demonstrating that mRNA translation is both sequential and selective during this process. The complete inhibition of the germination process in the presence of the translation inhibitor cycloheximide established that mRNA translation is critical for Arabidopsis seed germination. However, the dynamics of protein turnover and the selectivity of protein synthesis (mRNA translation) during Arabidopsis seed germination have not been addressed yet. Based on our detailed knowledge of the Arabidopsis seed proteome, we have deepened our understanding of seed mRNA translation during germination by combining twodimensional gel-based proteomics with dynamic radiolabeled proteomics using a radiolabeled amino acid precursor, namely [35 S]-methionine, in order to highlight de novo protein synthesis, stability, and turnover. Our data confirm that during early imbibition, the Arabidopsis translatome keeps reflecting an embryonic maturation program until a certain developmental checkpoint. Furthermore, by dividing the seed germination time lapse into discrete time windows, we highlight precise and specific patterns of protein synthesis. These data refine and deepen our knowledge of the three classical phases of seed germination based on seed water uptake during imbibition and reveal that selective mRNA translation is a key feature of seed germination. Beyond the quantitative control of translational activity, both the selectivity of mRNA translation and protein turnover appear as specific regulatory systems, critical for timing the molecular events leading to successful germination and seedling establishment. Molecular & Cellular Proteomics 13: 10.1074/mcp.M113.032227, 252-268, 2014.Seed germination is a vital stage in the plant life cycle during which embryo cells experience a programmed transition from a quiescent to a highly active metabolic state. Accordingly, seed quality in terms of germination vigor is of paramount importance for both ecological aspects and practical applications, as it influences the level, timing, and uniformity of seedling emergence in a wide range of environmental conditions (1, 2). In efforts to decipher the complex molecular mechanisms that control seed germination, genetic, genomic, and postgenomic analyses have been developed on the model plant Arabidopsis thaliana (3-6). Germination is classically described as a sequential time course divided into three major phases of seed water uptake (7). Phase I is characterized by rapid seed imbibition, which is crucial for the transition from the quiescent metabolic state of the dry seed to the high metabolic activity of the hydrated seed. Phase II corresponds to a period during which the seed imbibition level remains const...

show abstract

“…While export across the plasma membrane has been measured at the physiological level (Secor and Schrader, 1984;De Jong et al, 1997;Lesuffleur and Cliquet, 2010), no transporter has yet been identified that mediates this process (for review, see Okumoto and Pilot, 2011). The first cloned plant amino acid exporter, GAMMA AMINO BUTYRIC ACID PERMEASE (GABP), mediates g-aminobutyrate transport from the cytosol to the mitochondrion (Dü ndar and Bush, 2009;Michaeli et al, 2011). Because of its localization at the mitochondrial membrane, GABP is not expected to mediate amino acid export at the plasma membrane.…”

mentioning

confidence: 99%

The Ubiquitin E3 Ligase LOSS OF GDU2 Is Required for GLUTAMINE DUMPER1-Induced Amino Acid Secretion in Arabidopsis

et al. 2012

View full text Add to dashboard Cite

Amino acids serve as transport forms for organic nitrogen in the plant, and multiple transport steps are involved in cellular import and export. While the nature of the export mechanism is unknown, overexpression of GLUTAMINE DUMPER1 (GDU1) in Arabidopsis (Arabidopsis thaliana) led to increased amino acid export. To gain insight into GDU1's role, we searched for ethyl-methanesulfonate suppressor mutants and performed yeast-two-hybrid screens. Both methods uncovered the same gene, LOSS OF GDU2 (LOG2), which encodes a RING-type E3 ubiquitin ligase. The interaction between LOG2 and GDU1 was confirmed by glutathione S-transferase pull-down, in vitro ubiquitination, and in planta coimmunoprecipitation experiments. Confocal microscopy and subcellular fractionation indicated that LOG2 and GDU1 both localized to membranes and were enriched at the plasma membrane. LOG2 expression overlapped with GDU1 in the xylem and phloem tissues of Arabidopsis. The GDU1 protein encoded by the previously characterized intragenic suppressor mutant log1-1, with an arginine in place of a conserved glycine, failed to interact in the multiple assays, suggesting that the Gdu1D phenotype requires the interaction of GDU1 with LOG2. This hypothesis was supported by suppression of the Gdu1D phenotype after reduction of LOG2 expression using either artificial microRNAs or a LOG2 T-DNA insertion. Altogether, in accordance with the emerging bulk of data showing membrane protein regulation via ubiquitination, these data suggest that the interaction of GDU1 and the ubiquitin ligase LOG2 plays a significant role in the regulation of amino acid export from plant cells.

show abstract

A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism

Cited by 181 publications

References 51 publications

Model-based Confirmation of Alternative Substrates of Mitochondrial Electron Transport Chain

Model-based Confirmation of Alternative Substrates of Mitochondrial Electron Transport Chain

Dynamic Proteomics Emphasizes the Importance of Selective mRNA Translation and Protein Turnover during Arabidopsis Seed Germination

The Ubiquitin E3 Ligase LOSS OF GDU2 Is Required for GLUTAMINE DUMPER1-Induced Amino Acid Secretion in Arabidopsis

Contact Info

Product

Resources

About