Modeling of sensing potency of cytoskeletal systems decorated with metabolic enzymes

Oláh, Judit; Norris, Victor; Ovádi, Judit

doi:10.1016/j.jtbi.2014.10.018

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…The binding affinity depends on several factors, including phosphorylation status (Luther and Lee, 1986 ; Roberts and Somero, 1987 ; Pedrotti et al, 1996 ), the presence of other proteins, e.g., Microtubule Associated Proteins (MAPs) (Cortassa et al, 1994 ; Aon and Cortassa, 1997 ), or enzymatic activity (Cortassa and Aon, 1994 ; Vertessy et al, 1997 ; Cassimeris et al, 2012 ). Protein binding also affects microtubule and enzyme dynamics (Aon et al, 2001 ; Ovádi and Norris, 2013 ; Olah et al, 2015 ). The enhancement of metabolic flux depends upon several factors: (i) the presence for some enzymatic reactions of MAPs apart from tubulin; (ii) the concentration of microtubular protein (MTP); and (iii) the polymeric status (Cortassa et al, 1994 ).…”

Section: Cytoskeleton Organization and Metabolic Fluxesmentioning

confidence: 99%

Function of metabolic and organelle networks in crowded and organized media

Aon

Cortassa

2015

Front. Physiol.

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(Macro)molecular crowding and the ability of the ubiquitous cytoskeleton to dynamically polymerize–depolymerize are prevalent cytoplasmic conditions in prokaryotic and eukaryotic cells. Protein interactions, enzymatic or signaling reactions - single, sequential or in complexes - whole metabolic pathways and organelles can be affected by crowding, the type and polymeric status of cytoskeletal proteins (e.g., tubulin, actin), and their imparted organization. The self-organizing capability of the cytoskeleton can orchestrate metabolic fluxes through entire pathways while its fractal organization can frame the scaling of activities in several levels of organization. The intracellular environment dynamics (e.g., biochemical reactions) is dominated by the orderly cytoskeleton and the intrinsic randomness of molecular crowding. Existing evidence underscores the inherent capacity of intracellular organization to generate emergent global behavior. Yet unknown is the relative impact on cell function provided by organelle or functional compartmentation based on transient proteins association driven by weak interactions (quinary structures) under specific environmental challenges or functional conditions (e.g., hypoxia, division, differentiation). We propose a qualitative, integrated structural–functional model of cytoplasmic organization based on a modified version of the Sierspinsky–Menger–Mandelbrot sponge, a 3D representation of a percolation cluster, and examine its capacity to accommodate established experimental facts.

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Section: Cytoskeleton Organization and Metabolic Fluxesmentioning

confidence: 99%

Function of metabolic and organelle networks in crowded and organized media

Aon

Cortassa

2015

Front. Physiol.

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“…In the integrative sensor hypothesis, we have proposed that the cytoskeleton senses and integrates the general metabolic activity of the cell by binding metabolic enzymes and thereby changing its dynamics and its consumption of ATP and GTP. This binding would, in turn, depend on whether the enzyme catalyzes its cognate reaction [ 46 , 47 ]. A considerable body of evidence exists showing that some enzymes only bind to the cytoskeleton when it is active, whilst others only bind when inactive (for references see [ 46 ]).…”

Section: Speculative Strategies With the Potential To Treat Covid-19 And New Variantsmentioning

confidence: 99%

Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell

Norris

Ovádi

2021

Cells

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A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments.

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