Mitochondrial Oxidative Phosphorylation Is Regulated by Fructose 1,6-Bisphosphate

Díaz-Ruiz, Rodrigo; Avéret, Nicole; Araiza, Daniela; Pinson, Benoı̂t; Uribe‐Carvajal, Salvador; Devin, Anne; Rigoulet, Michel

doi:10.1074/jbc.m800408200

Cited by 128 publications

(105 citation statements)

References 53 publications

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“…As a consequence, yeast grown under conventional YPD medium (which contain 2% glucose) display a respirofermentative metabolism in which most of the glucose used is converted to ethanol. This phenomenon is known as the Crabtree effect (37,38). Yeast cells can also grow efficiently in rich medium containing glycerol (YPG), which is a nonfermentable carbon source.…”

Section: Resultsmentioning

confidence: 99%

Frataxin Depletion in Yeast Triggers Up-regulation of Iron Transport Systems before Affecting Iron-Sulfur Enzyme Activities

Moreno-Cermeño

Òbis

Bellı́

et al. 2010

Journal of Biological Chemistry

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The primary function of frataxin, a mitochondrial protein involved in iron homeostasis, remains controversial. Using a yeast model of conditional expression of the frataxin homologue YFH1, we analyzed the primary effects of YFH1 depletion. The main conclusion unambiguously points to the upregulation of iron transport systems as a primary effect of YFH1 down-regulation. We observed that inactivation of aconitase, an iron-sulfur enzyme, occurs long after the iron uptake system has been activated. Decreased aconitase activity should be considered part of a group of secondary events promoted by iron overloading, which includes decreased superoxide dismutase activity and increased protein carbonyl formation. Impaired manganese uptake, which contributes to superoxide dismutase deficiency, has also been observed in YFH1-deficient cells. This low manganese content can be attributed to the down-regulation of the metal ion transporter Smf2. Low Smf2 levels were not observed in AFT1/YFH1 double mutants, indicating that high iron levels could be responsible for the Smf2 decline. In summary, the results presented here indicate that decreased iron-sulfur enzyme activities in YFH1-deficient cells are the consequence of the oxidative stress conditions suffered by these cells.

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Section: Resultsmentioning

confidence: 99%

Frataxin Depletion in Yeast Triggers Up-regulation of Iron Transport Systems before Affecting Iron-Sulfur Enzyme Activities

Moreno-Cermeño

Òbis

Bellı́

et al. 2010

Journal of Biological Chemistry

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“…Taken together, these results indicate that besides the thermodynamic link between glycolysis and mitochondrial respiration (i.e. the cytosolic ATP/ADP and NADH/NADϩ ratio), a kinetic control of oxidative phosphorylation activity is exerted by the level of glycolytic sugar phosphates (18,23). This raises the question of a possible direct or indirect regulation of oxidative phosphorylation by the trehalose synthesis pathway.…”

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confidence: 85%

“…Thus, in a tps1⌬ mutant that is not able to grow on glucose (8,11,15), glucose addition to cells growing on galactose or on nonfermentable carbon sources induces a large increase in sugar phosphates and particularly in fructose 1,6-bisphosphate (8, 16 -18). Because fructose 1,6-bisphosphate is a potent inhibitor of respiration in Crabtree-positive yeast strains, such a huge increase in this compound must induce a strong inhibition of mitochondrial oxidative phosphorylation (18). Thus, through the control of glycolytic intermediate content, the trehalose synthesis pathway may be involved in the kinetic regulation of oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in a recent paper, we have shown that in yeast, low physiological concentrations of glucose 6-phosphate and fructose 6-phosphate slightly (20%) stimulate the respiratory flux and that this effect was strongly antagonized by Fru1,6bP (18). On the other hand, Fru1,6bP by itself is able to inhibit mitochondrial respiration only in mitochondria isolated from a Crabtree-positive strain.…”

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confidence: 99%

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The Trehalose Pathway Regulates Mitochondrial Respiratory Chain Content through Hexokinase 2 and cAMP in Saccharomyces cerevisiae

Noubhani

Bunoust

Bonini

et al. 2009

Journal of Biological Chemistry

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In yeast, trehalose is synthesized by a multimeric enzymatic complex: TPS1 encodes trehalose 6-phosphate synthase, which belongs to a complex that is composed of at least three other subunits, including trehalose 6-phosphate phosphatase Tps2 and the redundant regulatory subunits Tps3 and Tsl1. The product of the TPS1 gene plays an essential role in the control of the glycolytic pathway by restricting the influx of glucose into glycolysis. In this paper, we investigated whether the trehalose synthesis pathway could be involved in the control of the other energy-generating pathway: oxidative phosphorylation. We show that the different mutants of the trehalose synthesis pathway (tps1⌬, tps2⌬, and tps1,2⌬) exhibit modulation in the amount of respiratory chains, in terms of cytochrome content and maximal respiratory activity. Furthermore, these variations in mitochondrial enzymatic content are positively linked to the intracellular concentration in cAMP that is modulated by Tps1p through hexokinase2. This is the first time that a pathway involved in sugar storage, i.e. trehalose, is shown to regulate the mitochondrial enzymatic content.The control of glycolysis in the yeast Saccharomyces cerevisiae has been extensively studied. First, allosteric regulation of the irreversible steps catalyzed by phosphofructokinase (1), pyruvate kinase (review in Ref.2), and fructose-1,6-bisphosphatase (1) has been proposed, even though the overexpression of these key enzymes does not increase the glycolytic flux (3). Other mechanisms of control have been proposed such as futile cycle activity (4) and an inhibitory effect of ATP (5). Indeed, it seems likely that the regulation of glycolysis is a complex process involving different hierarchical events leading from gene expression to the metabolic fluxes via protein levels, enzyme activities, and metabolite effects (6, 7). Among these actors, the product of the TPS1 gene has been shown to play an essential role in the control of the glycolytic pathway by restricting the influx of glucose into glycolysis (8). TPS1 encodes trehalose 6-phosphate (Tre6P) 3 synthase (9 -12). This enzyme is part of a multimeric protein complex composed of at least three other subunits, i.e. Tre6P phosphatase encoded by TPS2 (13) and the redundant regulatory subunits Tps3 and Tsl1 (14).A particularly intriguing finding is that tps1⌬ mutants are defective not only for Tre6P synthesis but also for growth on glucose or related rapidly fermented sugars (8,11,15). This may be explained by an uncontrolled influx of glucose into the glycolytic pathway. This phenomenon is characterized by hyperaccumulation of glucose 6-phosphate, fructose 6-phosphate, and fructose 1,6-bisphosphate (Fru1,6bP) (8, 16 -18) and depletion of ATP, P i , and all intermediates of glycolysis downstream of glyceraldehyde-3-phosphate dehydrogenase (19). Several mutations have been described that suppress the growth defect of tps1⌬ mutants apparently by reducing sugar influx into glycolysis (16,20) or by diverting the excess sugar phosphate into ...

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“…Furthermore, accumulation of the glycolytic intermediate, fructose 1,6-biphosphate, directly inhibits mitochondrial respiration (69), again linking an increase in glycolytic flux to decreases in O 2 consumption.…”

Section: E) Metabolicmentioning

confidence: 99%

The Key Role of Nitric Oxide in Hypoxia: Hypoxic Vasodilation and Energy Supply–Demand Matching

Umbrello

Dyson²,

Feelisch³

et al. 2013

Antioxidants & Redox Signaling

105

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SIGNIFICANCE: A mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow -'hypoxic vasodilation' -occur in an attempt to restore oxygen supply. Nitric oxide is a major signalling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways).RECENT ADVANCES: This review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of nitric oxide, and mechanisms underlying the involvement of nitric oxide in hypoxic vasodilation. Recent insights into nitric oxide metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite reductases, and release of nitric oxide from storage pools. The processes through which nitric oxide levels are elevated during hypoxia are presented, namely (i) increased synthesis from nitric oxide synthases, increased reduction of nitrite to nitric oxide by heme-or pterin-based enzymes and increased release from nitric oxide stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase.CRITICAL ISSUES: Several reviews covered modulation of energetic metabolism by nitric oxide, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression FUTURE DIRECTIONS: We identify a key position for nitric oxide in the body's adaptation to an acute energy supply-demand mismatch.

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Mitochondrial Oxidative Phosphorylation Is Regulated by Fructose 1,6-Bisphosphate

Cited by 128 publications

References 53 publications

Frataxin Depletion in Yeast Triggers Up-regulation of Iron Transport Systems before Affecting Iron-Sulfur Enzyme Activities

Frataxin Depletion in Yeast Triggers Up-regulation of Iron Transport Systems before Affecting Iron-Sulfur Enzyme Activities

The Trehalose Pathway Regulates Mitochondrial Respiratory Chain Content through Hexokinase 2 and cAMP in Saccharomyces cerevisiae

The Key Role of Nitric Oxide in Hypoxia: Hypoxic Vasodilation and Energy Supply–Demand Matching

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