This Research Topic is a follow-up of the previous collection “Metabolic Modulation of Cellular Function.” While the previous topic focused on metabolites as sensors of cell status, mediators of cellular reactions, and substrates of post-translational and epigenetic modifications, this Topic will focus on metabolic pathway rewiring required to accommodate cell needs in the face of local perturbations in the metabolite balance and metabolic homeostasis.

Diseases, changes in dietary regimen, developmentally-driven changes in the local tissue milieu, immune responses, and other environmental changes impose significant shifts in the composition and balance of the metabolites composing tissue, interstitial, blood, and lymphatic metabolomes. Different works address the implications of these profound metabolomic changes on epigenetic gene regulation. For instance, ‘writers’ (methyltransferases) and ‘erasers’ (demethylases) of regulatory DNA methylation are regulated not only by the availability of methyl donors, but also by the levels of N-acetylglucosamine and alpha-ketoglutarate, as well as phosphorylation and acetylation reactions, all of which directly reflect the metabolome, which provides substrates for these covalent modifications. We invite original works that provide mechanistic insight into the links between these imposed environmental changes, subsequent modulation of the metabolome, and their regulatory consequences.

We welcome contributions in the form of research papers, communications, reviews, and opinions from researchers in the fields of disease metabolic research, systems biology, metabolic engineering, and more relevant fields. Works incorporating methodological novelties in areas such as spatial metabolomics are especially welcome.

Potential contributions are expected to include:

1) Mechanistic studies linking metabolic rewiring and pathway enrichments to nutrients availability. Within this subject matter, we will consider works addressing (but not limited to) changes in the balance between glycolysis and fatty acid metabolism, the link between amino acid availability and Krebs cycle activity, and links between pentose phosphate activity (NADPH production) and oxidative stress.

2) Metabolic rewiring in metabolic diseases (e.g., glycogen storage disorders, diabetes, ketoacidosis, Warburg effect and reverse Warburg effect in cancer metabolism, phenylketonuria, inborn errors of metabolism), especially works linking fuel preference (e.g., lipolysis v gluconeogenesis), aerobic glycolysis and ketogenesis to clinical severity, disease progression and therapy response.

Are you interested in contributing a manuscript to this Research Topic?

Metabolic Modulation of Cellular Function, vol II: Metabolic Pathway Rewiring