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Systemic redox regulation of cellular information processing.

ABSTRACT: Receptor-mediated signaling leads to transient changes in redox state, resulting in reversible oxidation of protein cysteine thiols. Numerous signaling proteins have been identified as being redox sensitive; however, to date, most investigations have focused on the ramifications of isolated protein modifications on cellular phenotypes. We propose that reversible thiol oxidation of proteins in a signaling network and their systemic interactions introduce features in the dynamics and control of cellular responses that are unique compared with isolated oxidative protein modifications. Simulations of dynamic redox regulation in different cellular contexts reveal feasible regulatory features for future experimental investigation. We suggest that location within a network, compartmentalization, and the degree of connectivity between redox proteins can dramatically modulate cellular information processing.

SUBMITTER: Dwivedi G

PROVIDER: S-EPMC3279717 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Systemic redox regulation of cellular information processing.

Dwivedi Gaurav G Kemp Melissa L ML

Antioxidants & redox signaling 20120201 4

Receptor-mediated signaling leads to transient changes in redox state, resulting in reversible oxidation of protein cysteine thiols. Numerous signaling proteins have been identified as being redox sensitive; however, to date, most investigations have focused on the ramifications of isolated protein modifications on cellular phenotypes. We propose that reversible thiol oxidation of proteins in a signaling network and their systemic interactions introduce features in the dynamics and control of ce ...[more]

PMID: 21939387

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Project description:One of the main aims of current biology is to understand the origin of the molecular organization that underlies the complex dynamic architecture of cellular life. Here, we present an overview of the main sources of biomolecular order and complexity spanning from the most elementary levels of molecular activity to the emergence of cellular systemic behaviors. First, we have addressed the dissipative self-organization, the principal source of molecular order in the cell. Intensive studies over the last four decades have demonstrated that self-organization is central to understand enzyme activity under cellular conditions, functional coordination between enzymatic reactions, the emergence of dissipative metabolic networks (DMN), and molecular rhythms. The second fundamental source of order is molecular information processing. Studies on effective connectivity based on transfer entropy (TE) have made possible the quantification in bits of biomolecular information flows in DMN. This information processing enables efficient self-regulatory control of metabolism. As a consequence of both main sources of order, systemic functional structures emerge in the cell; in fact, quantitative analyses with DMN have revealed that the basic units of life display a global enzymatic structure that seems to be an essential characteristic of the systemic functional metabolism. This global metabolic structure has been verified experimentally in both prokaryotic and eukaryotic cells. Here, we also discuss how the study of systemic DMN, using Artificial Intelligence and advanced tools of Statistic Mechanics, has shown the emergence of Hopfield-like dynamics characterized by exhibiting associative memory. We have recently confirmed this thesis by testing associative conditioning behavior in individual amoeba cells. In these Pavlovian-like experiments, several hundreds of cells could learn new systemic migratory behaviors and remember them over long periods relative to their cell cycle, forgetting them later. Such associative process seems to correspond to an epigenetic memory. The cellular capacity of learning new adaptive systemic behaviors represents a fundamental evolutionary mechanism for cell adaptation.

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Systemic redox regulation of cellular information processing.

Publications

Systemic redox regulation of cellular information processing.

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