Quantitative Analysis of Flux Regulation Through Hierarchical Regulation Analysis

Eunen, Karen van; Rossell, Sergio; Bouwman, Jildau; Westerhoff, Hans V.; Bakker, Barbara M.

doi:10.1016/b978-0-12-385118-5.00027-x

Cited by 15 publications

(15 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are not aware of other aging studies in which metabolic regulation has been quantified by Regulation Analysis. Metabolic regulation in microbes, however, has been extensively analysed (van Eunen, Rossell, Bouwman, Westerhoff, & Bakker, 2011) and is considered to be a large factor to explain observed flux changes. This makes sense, as metabolite concentrations are a direct readout of altered metabolic activity and therefore provide a more sensitive means of regulation than transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

et al. 2017

Self Cite

View full text Add to dashboard Cite

SummaryLoss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents. Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network.Mice were given a lifelong ad libitum low‐fat or high‐fat sucrose diet and were further divided into sedentary and running‐wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed. Subsequently, transcriptome was measured by RNA‐Seq and proteome by targeted LC‐MS/MS analysis with 13C‐labelled standards. In the sedentary groups, mitochondrial respiratory flux declined with age. Voluntary running protected the mitochondrial respiratory flux until 18 months of age. Beyond this time point, all groups converged. Regulation Analysis of flux, proteome and transcriptome showed that the decline of flux was equally regulated at the proteomic and at the metabolic level, while regulation at the transcriptional level was marginal. Proteomic regulation was most prominent at the beginning and at the end of the pathway, namely at the pyruvate dehydrogenase complex and at the synthesis and transport of ATP. Further proteomic regulation was scattered across the entire pathway, revealing an effective multisite regulation. Finally, reactions regulated at the protein level were highly overlapping between the four experimental groups, suggesting a common, post‐transcriptional mechanism of muscle aging.

show abstract

Section: Discussionmentioning

confidence: 99%

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, Other regulation coefficients in hormonal crosstalk network (Figure 1) can be derived based on the same principle. By quantifying the regulation coefficients, it is possible to quantify how each component regulates each flux or concentration in Figure 1, in a similar manner to the quantification of regulation in metabolic networks [18][19][20][21].…”

Section: Elucidating the Regulation Of Hormonal Crosstalk In Root Devmentioning

confidence: 99%

“…Regulation analysis for a metabolic pathway quantitatively dissects the extent to which the flux through an enzyme is regulated by changes in metabolic level or by changes in gene expression [18][19][20][21]. The principle of regulation analysis was described by Rossell et al [18].…”

Section: Regulation Analysismentioning

confidence: 99%

“…Following the methodologies developed for regulation analysis [18][19][20][21], regulation coefficients for auxin biosynthesis can be derived (eq 5): When ethylene is exogenously applied, the rate of auxin biosynthesis increases [22,23].…”

Section: Elucidating the Regulation Of Hormonal Crosstalk In Root Devmentioning

confidence: 99%

“…m  is the ''metabolic regulation coefficient'', quantifying the relative contribution of changes in the interaction of the enzyme with the rest of metabolism to the regulation of the enzyme's flux [18][19][20][21].…”

Section: Regulation Analysismentioning

confidence: 99%

See 2 more Smart Citations

Elucidating the regulation of complex signalling systems in plant cells

Liu

Lindsey

Hussey

2014

Biochemical Society Transactions

View full text Add to dashboard Cite

Additional information:Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details.

show abstract

Mitoenergetic Dysfunction Triggers a Rapid Compensatory Increase in Steady-State Glucose Flux

Liemburg-Apers

Schirris

Rüssel

et al. 2015

Biophysical Journal

View full text Add to dashboard Cite

ATP can be produced in the cytosol by glycolytic conversion of glucose (GLC) into pyruvate. The latter can be metabolized into lactate, which is released by the cell, or taken up by mitochondria to fuel ATP production by the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS) system. Altering the balance between glycolytic and mitochondrial ATP generation is crucial for cell survival during mitoenergetic dysfunction, which is observed in a large variety of human disorders including cancer. To gain insight into the kinetic properties of this adaptive mechanism we determined here how acute (30 min) inhibition of OXPHOS affected cytosolic GLC homeostasis. GLC dynamics were analyzed in single living C2C12 myoblasts expressing the fluorescent biosensor FLII(12)Pglu-700μδ6 (FLII). Following in situ FLII calibration, the kinetic properties of GLC uptake (V1) and GLC consumption (V2) were determined independently and used to construct a minimal mathematical model of cytosolic GLC dynamics. After validating the model, it was applied to quantitatively predict V1 and V2 at steady-state (i.e., when V1 = V2 = Vsteady-state) in the absence and presence of OXPHOS inhibitors. Integrating model predictions with experimental data on lactate production, cell volume, and O2 consumption revealed that glycolysis and mitochondria equally contribute to cellular ATP production in control myoblasts. Inhibition of OXPHOS induced a twofold increase in Vsteady-state and glycolytic ATP production flux. Both in the absence and presence of OXPHOS inhibitors, GLC was consumed at near maximal rates, meaning that GLC consumption is rate-limiting under steady-state conditions. Taken together, we demonstrate here that OXPHOS inhibition increases steady-state GLC uptake and consumption in C2C12 myoblasts. This activation fully compensates for the reduction in mitochondrial ATP production, thereby maintaining the balance between cellular ATP supply and demand.

show abstract

Quantitative Analysis of Flux Regulation Through Hierarchical Regulation Analysis

Cited by 15 publications

References 64 publications

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

Elucidating the regulation of complex signalling systems in plant cells

Mitoenergetic Dysfunction Triggers a Rapid Compensatory Increase in Steady-State Glucose Flux

Contact Info

Product

Resources

About