Mitochondrial neutral amino acid transport: evidence for a carrier mediated mechanism

Cybulski, Raymond L.; Fisher, Ronald R.

doi:10.1021/bi00642a026

Cited by 41 publications

(19 citation statements)

References 32 publications

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“…In terms of molecular mechanisms, it is reasonable to assume that the protective effects of Met are linked to its structural similarities with the MeHg–Cys complex. This idea is in agreement with the existence of a mitochondrial neutral amino acid transport (Raymond et al, 1977), which is likely responsible for the uptake of MeHg (as MeHg–Cys complex) into mitochondria. Based on our results, it is possible to state that LAT is not only important for the transport of MeHg into the cell, but also for the transport of MeHg within cellular organelles, allowing for the occurrence of mitochondrial toxicity probably due to the direct effects of MeHg in mitochondrial proteins.…”

Section: Discussionsupporting

confidence: 86%

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Roos

Puntel

Farina

et al. 2011

Toxicology and Applied Pharmacology

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Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg–Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg–Cys complex. The liver slices were pre-treated with Met (250 μM) 15 min before being exposed to MeHg (25 μM) or MeHg–Cys (25 μM each) for 30 min at 37 °C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg–Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg–Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg–Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg–Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg–Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg-and/or MeHg–Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the competition of Met with the complex formed between MeHg and endogenous cysteine. In summary, our results show that Met pre-treatment produces pronounced protection against the toxic effects induced by MeHg and/or the MeHg–Cys complex on mitochondrial function and cell viability. Consequently, this amino acid offers considerable promise as a potential agent for treating acute MeHg exposure.

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Section: Discussionsupporting

confidence: 86%

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Roos

Puntel

Farina

et al. 2011

Toxicology and Applied Pharmacology

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“…The characteristics of the neutral amino acid carrier in mung bean mitochondria are quite similar to those in rat liver mitochondria (3,7,13,17). Comparatively, the mung bean system is more sensitive to p-mercuribenzoate and mersalyl inhibition but exhibits a lesser degree of stereospecificity.…”

Section: Discussionmentioning

confidence: 69%

Carrier Protein-mediated Transport of Neutral Amino Acids into Mung Bean Mitochondria

Cavalieri

Huang²

1980

Plant Physiol.

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The transport of neutral amino acids into mitochondria isolated from the hypocotyl of mung bean (Roxb.) was studied by the swelling technique. Isolated mitochondria sweled when added to an isosmotic solution of proline, serine, methionine, threonine, alanine, and glycine. The swelling was stereospecific in that it was faster in the L-amino acid than in the corresponding D-amino acid. Preincubation of the mitochondria with the sulfhydryl modifying reagents,p-mercuribenzoate and mersalyl, resulted in an inhibition of the swelling caused by proline, serine, threonine, and glycine. The sweling induced by alanine was inhibited only by mersalyl, whereas that by methionine was inhibited only byp-mercuribenzoate. In all cases, the inhibition caused by the sulfhydryl modifying reagents was readily reversible by the subsequent treatment of the mitochondria with dithiothreitol. N-Ethylmaleimide, another sulfhydryl-modifying reagent, did not cause any inhibition of the swelling. The findings indicate the existence of a protein mediated mechanism for the transport of neutral amino acids into plant mitochondria.In plant cells, numerous metabolic events involving the reactions of neutral amino acids occur inside the mitochondria. The interconversion of serine to glycine and a one-carbon fragment in the mitochondria is well-documented (6,16,20). Since the mitochondria contain several aminotransferases specific for some neutral amino acids (25), the interconversion of these amino acids with their corresponding keto acids should occur inside the organelles. In addition, there are two major metabolic events involving mitochondrial metabolism of neutral amino acids that are unique to higher plants. One of them is the operation of the glycolate pathway in leaves during photorespiration (16,24). In this pathway, glycine formed in the leaf peroxisomes enters the mitochondria and is oxidized to form C02, NH3, and a one-carbon fragment which will join with another glycine to form a serine; serine subsequently leaves the mitochondria to be converted to sugar eventually. The other metabolic event is proline metabolism in connection with the accumulation of proline under environmental stresses (2,4,14,23). Although the detailed mechanism of proline metabolism is still unclear, it is known that the enzymes of proline catabolism are localized in the mitochondria, whereas the anabolic enzymes are present in the cytosol (1, 2,15,23

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“…In agreement with this proposal, the NMR studies of isolated mitochondria provide direct evidence for the export of OAS from mitochondria. Neutral amino acids have been shown to permeate across the mitochondrial membranes by carrierand/or channel-mediated processes (30,31). To date, however, the identities of the mitochondrial OAS exporter and the transporters for serine and most other amino acids remain unknown in plants (32).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Cysteine Synthase Complex Regulates O-Acetylserine Biosynthesis in Plants

Wirtz

Beard

Lee

et al. 2012

Journal of Biological Chemistry

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Background: Cysteine biosynthesis is the exclusive entry point for reduced sulfur in cellular metabolism. Results: The mitochondrial cysteine synthase complex (mCSC) regulates serine acetyltransferase activity in response to cysteine availability. Conclusion:The mCSC is a sensor of sulfur availability and regulates cysteine synthesis. Significance: The integration of cysteine in the regulatory model of the CSC establishes a new sensory function for the mCSC.

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Mitochondrial neutral amino acid transport: evidence for a carrier mediated mechanism

Cited by 41 publications

References 32 publications

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Carrier Protein-mediated Transport of Neutral Amino Acids into Mung Bean Mitochondria

Mitochondrial Cysteine Synthase Complex Regulates O-Acetylserine Biosynthesis in Plants

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