bims-meprid 2023-12-24 papers

Issue of 2023‒12‒24
two papers selected by
Alessandro Carrer, Veneto Institute of Molecular Medicine

Cell Metab. 2023 Dec 12. pii: S1550-4131(23)00460-6. [Epub ahead of print]

Nutrient inputs and social metabolic control of T cell fate.

Zachary A Bacigalupa, Madelyn D Landis, Jeffrey C Rathmell.

Cells in multicellular organisms experience diverse neighbors, signals, and evolving physical environments that drive functional and metabolic demands. To maintain proper development and homeostasis while avoiding inappropriate cell proliferation or death, individual cells interact with their neighbors via "social" cues to share and partition available nutrients. Metabolic signals also contribute to cell fate by providing biochemical links between cell-extrinsic signals and available resources. In addition to metabolic checkpoints that sense nutrients and directly supply molecular intermediates for biosynthetic pathways, many metabolites directly signal or provide the basis for post-translational modifications of target proteins and chromatin. In this review, we survey the landscape of T cell nutrient sensing and metabolic signaling that supports proper immunity while avoiding immunodeficiency or autoimmunity. The integration of cell-extrinsic microenvironmental cues with cell-intrinsic metabolic signaling provides a social metabolic control model to integrate cell signaling, metabolism, and fate.

Keywords: T cells; epigenetics; immunometabolism; metabolic signaling; social control model

DOI: https://doi.org/10.1016/j.cmet.2023.12.009

J Biol Chem. 2023 Dec 13. pii: S0021-9258(23)02591-7. [Epub ahead of print] 105563

Metabolic transitions regulate global protein fatty acylation.

Manasi Talwadekar, Subhash Khatri, Chinthapalli Balaji, Arnab Chakraborty, Nandini-Pal Basak, Siddhesh Kamat, Ullas Kolthur-Seetharam.

Intermediary metabolites and flux through various pathways have emerged as key determinants of post-translational modifications. Independently, dynamic fluctuations in their concentrations are known to drive cellular energetics in a bi-directional manner. Notably, intracellular fatty acid pools that drastically change during fed and fasted states act as precursors for both ATP production and fatty acylation of proteins. Protein fatty acylation is well regarded for its role in regulating structure and functions of diverse proteins, however the effect of intracellular concentrations of fatty acids on protein modification is less understood. In this regard, we unequivocally demonstrate that metabolic contexts, viz. fed and fasted states, dictate the extent of global fatty acylation. Moreover, we show that presence or absence of glucose, that influences cellular and mitochondrial uptake/utilization of fatty acids, affects palmitoylation and oleoylation, which is consistent with their intracellular abundance in fed and fasted states. Employing complementary approaches including click-chemistry, lipidomics and imaging, we show the top-down control of cellular metabolic state. Importantly, our results establish the crucial role of mitochondria and retrograde signaling components like SIRT4, AMPK and mTOR in orchestrating protein fatty acylation at a whole cell level. Specifically, pharmacogenetic perturbations that alter either mitochondrial functions and/or retrograde signaling affect protein fatty acylation. Besides illustrating the cross-talk between carbohydrate and lipid metabolism in mediating bulk post-translational modification, our findings also highlight the involvement of mitochondrial energetics.

Keywords: Acylation; acyl exchange; free fatty acids; oleate; palmitate; sirtuins

DOI: https://doi.org/10.1016/j.jbc.2023.105563