Mitochondrial involvement to methylglyoxal detoxification: d-Lactate/Malate antiporter in Saccharomyces cerevisiae

Pallotta, Maria Luigia

doi:10.1007/s10482-012-9724-0

Cited by 13 publications

(9 citation statements)

References 55 publications

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“…Cells grown in 5% glucose SD medium produced 2.4-fold more D-lactate by 4.5 h than cells grown in 0.5% glucose medium ( Figure 3C). Mitochondrial metabolism of D-lactate has been reported (Pallotta, 2012) but is unlikely to contribute to depletion of accumulating D-lactate while glucose is present, based on the observation that in all experiments D-lactate continued to accumulate in the media of cells grown in the presence of glucose until media glucose was depleted. When glucose was depleted from the media, cells then utilized D-lactate as the carbon source ( Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

“…Methylglyoxal can also be be metabolized by NADH-dependent alcohol dehydrogenase in yeast (Chen et al, 2003). The relative contributions of the glyoxalase pathway and aldose reductase to methylglyoxal detoxification remain poorly characterized and likely vary, depending on strains selected and growth conditions (Pallotta, 2012). Figure 1 provides an overview of the major metabolic pathways associated with methyglyoxal production and metabolism in S. cerevisiae as a consequence of glucose metabolism.…”

Section: Introductionmentioning

confidence: 99%

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D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

Stewart

Navid

Kulp

et al. 2013

Yeast

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Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae grown in media containing low, moderate, and high glucose concentrations to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log-phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high-glucose media resulted in increased generation of the methylglyoxal metabolite D-lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high-glucose media maintained higher glucose uptake flux than cells grown in moderate-glucose or low-glucose media. Computational modeling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD+/NADH ratio.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

Stewart

Navid

Kulp

et al. 2013

Yeast

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“…9). Even otherwise, cytoplasm-generated D-lactate is also known to translocate to mitochondria for its metabolism to pyruvate by the mitochondrial D-LDH proteins [54]. Nonetheless, even cytoplasmic D-LDH proteins were predicted in the sorghum genome and included SbDLDH-3 and SbDLDH-4 proteins ( Fig.…”

Section: Discussionmentioning

confidence: 99%

From methylglyoxal to pyruvate: a genome-wide study for the identification of glyoxalases and D-lactate dehydrogenases in Sorghum bicolor

et al. 2020

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Background: The glyoxalase pathway is evolutionarily conserved and involved in the glutathione-dependent detoxification of methylglyoxal (MG), a cytotoxic by-product of glycolysis. It acts via two metallo-enzymes, glyoxalase I (GLYI) and glyoxalase II (GLYII), to convert MG into D-lactate, which is further metabolized to pyruvate by D-lactate dehydrogenases (D-LDH). Since D-lactate formation occurs solely by the action of glyoxalase enzymes, its metabolism may be considered as the ultimate step of MG detoxification. By maintaining steady state levels of MG and other reactive dicarbonyl compounds, the glyoxalase pathway serves as an important line of defence against glycation and oxidative stress in living organisms. Therefore, considering the general role of glyoxalases in stress adaptation and the ability of Sorghum bicolor to withstand prolonged drought, the sorghum glyoxalase pathway warrants an in-depth investigation with regard to the presence, regulation and distribution of glyoxalase and D-LDH genes. Result: Through this study, we have identified 15 GLYI and 6 GLYII genes in sorghum. In addition, 4 D-LDH genes were also identified, forming the first ever report on genome-wide identification of any plant D-LDH family. Our in silico analysis indicates homology of putatively active SbGLYI, SbGLYII and SbDLDH proteins to several functionally characterised glyoxalases and D-LDHs from Arabidopsis and rice. Further, these three gene families exhibit development and tissue-specific variations in their expression patterns. Importantly, we could predict the distribution of putatively active SbGLYI, SbGLYII and SbDLDH proteins in at least four different sub-cellular compartments namely, cytoplasm, chloroplast, nucleus and mitochondria. Most of the members of the sorghum glyoxalase and D-LDH gene families are indeed found to be highly stress responsive.Conclusion: This study emphasizes the role of glyoxalases as well as that of D-LDH in the complete detoxification of MG in sorghum. In particular, we propose that D-LDH which metabolizes the specific end product of glyoxalases pathway is essential for complete MG detoxification. By proposing a cellular model for detoxification of MG via glyoxalase pathway in sorghum, we suggest that different sub-cellular organelles are actively involved in MG metabolism in plants.

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“…However, in S. cerevisiae it is a substrate for different isoforms of D-lactate dehydrogenase [218]. Also, in yeast it was recently discovered that mitochondria can uptake D-lactate, metabolize it and export newly synthesized malate through a putative D-lactate/malate antiport mechanism [219]. Whether this is a regulatory mechanism to decrease the methylglyoxal concentration from the cytosol or an alternative pathway to produce malate for gluconeogenesis is still an open question.…”

Section: Enzymes Lost In Metabolismmentioning

confidence: 99%

The glyoxalase pathway: the first hundred years… and beyond

Silva

Gomes

Ferreira

et al. 2013

Biochemical Journal

222

207

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The discovery of the enzymatic formation of lactic acid from methylglyoxal dates back to 1913 and was believed to be associated with one enzyme termed ketonaldehydemutase or glyoxalase, the latter designation prevailed. However, in 1951 it was shown that two enzymes were needed and that glutathione was the required catalytic co-factor. The concept of a metabolic pathway defined by two enzymes emerged at this time. Its association to detoxification and anti-glycation defence are its presently accepted roles, since methylglyoxal exerts irreversible effects on protein structure and function, associated with misfolding. This functional defence role has been the rationale behind the possible use of the glyoxalase pathway as a therapeutic target, since its inhibition might lead to an increased methylglyoxal concentration and cellular damage. However, metabolic pathway analysis showed that glyoxalase effects on methylglyoxal concentration are likely to be negligible and several organisms, from mammals to yeast and protozoan parasites, show no phenotype in the absence of one or both glyoxalase enzymes. The aim of the present review is to show the evolution of thought regarding the glyoxalase pathway since its discovery 100 years ago, the current knowledge on the glyoxalase enzymes and their recognized role in the control of glycation processes.

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Mitochondrial involvement to methylglyoxal detoxification: d-Lactate/Malate antiporter in Saccharomyces cerevisiae

Cited by 13 publications

References 55 publications

D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

From methylglyoxal to pyruvate: a genome-wide study for the identification of glyoxalases and D-lactate dehydrogenases in Sorghum bicolor

The glyoxalase pathway: the first hundred years… and beyond

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