A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status

Lenzen, Sigurd

doi:10.1074/jbc.r114.557314

Cited by 129 publications

(96 citation statements)

References 65 publications

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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

View full text Add to dashboard Cite

show abstract

“…Glycolysis is a common catabolic pathway for most of life, especially for anaerobic bacteria and cancer cells. However, it is not an efficient pathway to generate ATP, and excessive glycolysis can cause a huge waste of glucose in tissue (Lenzen, 2014). In addition, the lactic acid product also causes damage for animals.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

Sun

Huang

Yin

et al. 2016

Animal

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Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.Keywords: lipopolysaccharide, mitochondria, glycolysis, pig, inflammation ImplicationsSkeletal muscle is the primary tissue responsible for wholebody energy metabolism. In the current study, we designed the experiment to investigate the effect of lipopolysaccharide (LPS) treatment on muscle energy metabolism in pigs. The results indicated that LPS treatment significantly changed glycolysis level and mitochondrial function in the longissimus dorsi (LD) muscle of pigs, and increased calcium content induced by endoplasm reticulum stress was possibly involved. Understanding these underlying mechanisms may provide new therapeutic strategies for treating metabolic diseases induced by LPS in muscle.

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“…F2,6BP acts to activate PFK-1 and to lower the threshold for glycolytic oscillations (292,348). In addition to controlling F2,6BP levels, PFK/FBPase2 binds to, and activates, glucokinase, apparently by physical interaction rather than enzymatic activity (292).…”

Section: A Glycolytic Oscillatormentioning

confidence: 99%

The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

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The pancreatic ␤-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field.

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A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status

Cited by 129 publications

References 65 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

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

The Pancreatic β-Cell: A Bioenergetic Perspective

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