Series |

Metabolic signalling

Metabolic regulation lies at the intersection of many research fields, including biochemistry, molecular and cell biology, physiology and the study of disease pathogenesis. Numerous advances have been made in our understanding of how metabolic pathways can be dynamically regulated by cellular events to meet the energy needs of the cell and maintain cell and organismal homeostasis. Dysregulation of these pathways, which influence signal transduction and gene expression, is linked to metabolic diseases such as obesity and type 2 diabetes, as well as to cancer and ageing.

This series features Review articles that discuss various aspects of the regulation of metabolic signalling, the interface between metabolic regulators and cellular processes and the implications of their deregulation for human diseases.


  • Nature Reviews Molecular Cell Biology | Review Article

    Metabolomics and lipidomics have enabled the identification of metabolites (such as lipids, amino acids and bile acids) and metabolic pathways that modulate insulin sensitivity both directly and indirectly. Understanding the metabolic adaptations involved in insulin resistance may lead to novel approaches for preventing and treating T2DM.

    • Qin Yang
    • , Archana Vijayakumar
    •  &  Barbara B. Kahn
  • Nature Reviews Molecular Cell Biology | Review Article

    Metabolism feeds into gene regulation, allowing adaptation of gene expression to satisfy cellular needs, including in pathological scenarios such as cancer. Metabolism modulates gene expression through metabolites, which serve as cofactors for DNA and histone modifiers, and through metabolic enzymes, which locally regulate chromatin and transcription in the nucleus.

    • Xinjian Li
    • , Gabor Egervari
    • , Yugang Wang
    • , Shelley L. Berger
    •  &  Zhimin Lu
  • Nature Reviews Molecular Cell Biology | Review Article

    Research over the past few decades has elucidated the biochemical mechanisms underlying insulin receptor signalling. Recent insights into the complexity of its temporal and tissue-specific regulation, which involves various combinations of signalling modules in different cell types, are shedding light on the pleiotropic effects of insulin action and the pathogenesis of insulin resistance.

    • Rebecca A. Haeusler
    • , Timothy E. McGraw
    •  &  Domenico Accili
  • Nature Reviews Molecular Cell Biology | Review Article

    AMP-activated protein kinase (AMPK) senses cellular energy levels and phosphorylates a variety of cellular substrates to inhibit or stimulate anabolic and catabolic processes, adjusting metabolism to energy needs. Recent studies have uncovered a crucial role of AMPK in the regulation of mitochondrial dynamics and mitophagy, further expanding its role in the control of cellular metabolism.

    • Sébastien Herzig
    •  &  Reuben J. Shaw
  • Nature Reviews Molecular Cell Biology | Review Article

    Lipolysis degrades triacylglycerols to supply cells with free fatty acids, which are essential components of membrane lipids and substrates for energy production. Recent discoveries transformed our understanding of the functions of and crosstalk between 'neutral' lipolysis, which occurs in the cytosol, and lipophagy and 'acid' lipolysis, which occur in lysosomes, and how dysfunction in these processes contributes to metabolic diseases.

    • Rudolf Zechner
    • , Frank Madeo
    •  &  Dagmar Kratky
  • Nature Reviews Molecular Cell Biology | Review Article

    Sirtuins are NAD+-dependent protein deacylases that can reverse various aspects of ageing in model organisms. Trials in non-human primates and humans indicate that sirtuin-activating compounds (STACs) and NAD+ precursors are safe and effective in treating inflammatory and metabolic disorders, thereby holding great potential to treat various diseases and to extend lifespan in humans.

    • Michael S. Bonkowski
    •  &  David A. Sinclair