A Differential Redox Regulation of the Pathways Metabolizing Glyceraldehyde-3-Phosphate Tunes the Production of Reducing Power in the Cytosol of Plant Cells

Piattoni, Claudia Vanesa; Guerrero, Sandra; Iglesias, Alberto A.

doi:10.3390/ijms14048073

Cited by 37 publications

(39 citation statements)

References 44 publications

(76 reference statements)

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“…Several regulatory mechanisms controlling respiratory fluxes have been identified. They include the modulation of the activity of key enzymes either by an inhibitory effect of high concentration of the products (Wegener and Krause, 2002;Lenzen, 2014) or by posttranslational modifications such as phosphorylation or redox regulation (Piattoni et al, 2013;Ros and Schulze, 2013;Lushchak et al, 2014;Schmidtmann et al, 2014). Our data suggest an additional regulatory feedback loop involving complex I activity.…”

Section: Regulation Of Respiratory Pathwaysmentioning

confidence: 80%

Complete Mitochondrial Complex I Deficiency Induces an Up-Regulation of Respiratory Fluxes That Is Abolished by Traces of Functional Complex I

Kühn

Obata²,

Feher³

et al. 2015

Plant Physiol.

110

122

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Complex I (NADH:ubiquinone oxidoreductase) is central to cellular NAD + recycling and accounts for approximately 40% of mitochondrial ATP production. To understand how complex I function impacts respiration and plant development, we isolated Arabidopsis (Arabidopsis thaliana) lines that lack complex I activity due to the absence of the catalytic subunit NDUFV1 (for NADH:ubiquinone oxidoreductase flavoprotein1) and compared these plants with ndufs4 (for NADH:ubiquinone oxidoreductase Fe-S protein4) mutants possessing trace amounts of complex I. Unlike ndufs4 plants, ndufv1 lines were largely unable to establish seedlings in the absence of externally supplied sucrose. Measurements of mitochondrial respiration and ATP synthesis revealed that compared with ndufv1, the complex I amounts retained by ndufs4 did not increase mitochondrial respiration and oxidative phosphorylation capacities. No major differences were seen in the mitochondrial proteomes, cellular metabolomes, or transcriptomes between ndufv1 and ndufs4. The analysis of fluxes through the respiratory pathway revealed that in ndufv1, fluxes through glycolysis and the tricarboxylic acid cycle were dramatically increased compared with ndufs4, which showed near wild-type-like fluxes. This indicates that the strong growth defects seen for plants lacking complex I originate from a switch in the metabolic mode of mitochondria and an up-regulation of respiratory fluxes. Partial reversion of these phenotypes when traces of active complex I are present suggests that complex I is essential for plant development and likely acts as a negative regulator of respiratory fluxes.In most eukaryotic organisms, energy is mainly provided by cellular respiration, which is composed of three main pathways. Glycolysis in the cytosol, and additionally in the plastids of plants, degrades sugars into pyruvate. The tricarboxylic acid (TCA) cycle, which largely resides in the mitochondrial matrix, further dissimilates pyruvate into CO 2 . These two pathways generate reduced cofactors, mostly NADH. The oxidative phosphorylation (OXPHOS) system couples cofactor recycling with ATP production. The electron transfer chain (ETC) located in the mitochondrial inner membrane (IM) uses the redox energy of the reduced cofactors to create an electrochemical gradient across the IM. This gradient is then used by the ATP synthase to convert ADP to ATP, which is subsequently exported from the mitochondria to fuel cellular metabolism and sustain housekeeping functions and growth.The ETC is composed of four large multiprotein complexes. The first of these complexes is the NADHubiquinone oxidoreductase, also called complex I. It plays a crucial role in recycling NAD + for the TCA cycle, and its activity is responsible for about 40% of the total proton pumping across the IM (Wikström, 1984;Galkin et al., 2006). In plants, additional NADH dehydrogenases located on both sides of the IM are present (for review, see Rasmusson et al., 2008). These enzymes can recycle NAD + for use in glycolysis and the TCA cyc...

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Section: Regulation Of Respiratory Pathwaysmentioning

confidence: 80%

Complete Mitochondrial Complex I Deficiency Induces an Up-Regulation of Respiratory Fluxes That Is Abolished by Traces of Functional Complex I

Kühn

Obata²,

Feher³

et al. 2015

Plant Physiol.

110

122

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“…In the cytosol of plant cells, a non-phosphorylating GAPDH exists, namely NP-GAPDH, which is irreversibly oxidizing G3P yielding 3-PGA directly, and not 1,3-bisPGA that would allow for ATP formation in a next step. Interestingly, NP-GAPDH is found to be 63 times less sensitive to oxidative modification and subsequent inactivation than is GapC (Piattoni et al, 2013). NP-GAPDH is thought to produce NADPH, when GapC is inactivated under oxidative stress.…”

Section: Gapdh Functions In Primary Metabolismmentioning

confidence: 99%

“…Upon light stress, this can be either photoacclimation or cell death (Mullineaux et al, 2006). H 2 O 2 is sensed already at low levels and leads to the induction of either antioxidant systems or of genes for re-routing of metabolic pathways in order to cope with changed demand for electron acceptors for maintenance of redox homeostasis (Piattoni et al, 2013;Selinski and Scheibe, 2014).…”

Section: Role Of Gapdh In Acclimation and Cell Protectionmentioning

confidence: 99%

Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?

Hildebrandt¹,

Knuesting²,

Berndt³

et al. 2015

Biological Chemistry

148

131

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Cytosolic glyceraldehyde 3-phosphate dehydrogenase (GAPDH, E.C. 1.2.1.12) is present in all organisms and catalyzes the oxidation of triose phosphate during glycolysis. GAPDH is one of the most prominent cellular targets of oxidative modifications when reactive oxygen and nitrogen species are formed during metabolism and under stress conditions. GAPDH harbors a strictly conserved catalytic cysteine, which is susceptible to a variety of thiol modifications, including S-sulfenylation, S-glutathionylation, S-nitrosylation, and S-sulfhydration. Upon reversible oxidative thiol modification of GAPDH, glycolysis is inhibited leading to a diversion of metabolic flux through the pentose-phosphate cycle to increase NADPH production. Furthermore, oxidized GAPDH may adopt new functions in different cellular compartments including the nucleus, as well as in new microcompartments associated with the cytoskeleton, mitochondria and plasma membrane. This review focuses on the recently discovered mechanism underlying the eminent reactivity between GAPDH and hydrogen peroxide and the subsequent redox-dependent moonlighting functions discriminating between the induction either of adaptive responses and adjustment of metabolism or of cell death in yeast, plants, and mammals. In light of the summarized results, cytosolic GAPDH might function as a sensor for redox signals and an information hub to transduce these signals for appropriate responses.

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“…GAPDH is the prototype moonlighting protein in animal and plant cells, exhibiting activities distinct from its classically identified function in glycolysis, such as DNA stability, control of gene expression, autophagy and apoptosis (Sirover 2014). GAPDH fulfills alternative non-metabolic functions triggered by redox post-translational modifications, such as glutathionylation (Bedhomme et al 2012), S-nitrosylation ) and cysteine oxidation (Piattoni et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Regulates the Cytosolic/Nuclear Partitioning of Glyceraldehyde-3-Phosphate Dehydrogenase by Enhancing its Nuclear Localization

Aroca

Schneider

Scheibe

et al. 2017

Plant and Cell Physiology

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Hydrogen sulfide is an important signaling molecule comparable with nitric oxide and hydrogen peroxide in plants. The underlying mechanism of its action is unknown, although it has been proposed to be S-sulfhydration. This post-translational modification converts the thiol groups of cysteines within proteins to persulfides, resulting in functional changes of the proteins. In Arabidopsis thaliana, Ssulfhydrated proteins have been identified, including the cytosolic isoforms of glyceraldehyde-3-phosphate dehydrogenase GapC1 and GapC2. In this work, we studied the regulation of sulfide on the subcellular localization of these proteins using two different approaches. We generated GapC1-green fluorescent protein (GFP) and GapC2-GFP transgenic plants in both the wild type and the des1 mutant defective in the L-cysteine desulfhydrase DES1, responsible for the generation of sulfide in the cytosol. The GFP signal was detected in the cytoplasm and the nucleus of epidermal cells, although with reduced nuclear localization in des1 compared with the wild type, and exogenous sulfide treatment resulted in similar signals in nuclei in both backgrounds. The second approach consisted of the immunoblot analysis of the GapC endogenous proteins in enriched nuclear and cytosolic protein extracts, and similar results were obtained. A significant reduction in the total amount of GapC in des1 in comparison with the wild type was determined and exogenous sulfide significantly increased the protein levels in the nuclei in both plants, with a stronger response in the wild type. Moreover, the presence of an Ssulfhydrated cysteine residue on GapC1 was demonstrated by mass spectrometry. We conclude that sulfide enhances the nuclear localization of glyceraldehyde-3-phosphate dehydrogenase.

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A Differential Redox Regulation of the Pathways Metabolizing Glyceraldehyde-3-Phosphate Tunes the Production of Reducing Power in the Cytosol of Plant Cells

Cited by 37 publications

References 44 publications

Complete Mitochondrial Complex I Deficiency Induces an Up-Regulation of Respiratory Fluxes That Is Abolished by Traces of Functional Complex I

Complete Mitochondrial Complex I Deficiency Induces an Up-Regulation of Respiratory Fluxes That Is Abolished by Traces of Functional Complex I

Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?

Hydrogen Sulfide Regulates the Cytosolic/Nuclear Partitioning of Glyceraldehyde-3-Phosphate Dehydrogenase by Enhancing its Nuclear Localization

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