Volume 5 Issue 11, November 2023

In 1923, Otto Warburg published his landmark study, in which he described his seminal observations related to metabolic shifts in cancer, often referred to as the Warburg effect. His work laid the foundation for an understanding of how metabolic reconfiguration contributes to cancer onset and progression. Several researchers in the field share their thoughts on what this discovery means to them and how it has inspired their scientific journey.

By analysing the effect of disrupting microbiota during in vivo reprogramming, Kovatcheva et al. demonstrated that vitamin B₁₂-dependent metabolism is a limiting factor for cellular reprogramming and plasticity, and propose its therapeutic supplementation for the improvement of tissue repair.

Mitochondrial proteins are frequently acetylated, but most of these modifications are thought to occur non-enzymatically, rather than requiring an acetyltransferase. A new study by Akhtar and colleagues challenges this view by demonstrating that MOF, a well-characterized histone acetyltransferase, bolsters mitochondrial metabolism by acetylating the complex IV assembly factor COX17.

Group 3 innate lymphoid cells (ILC3s) maintain intestinal barrier integrity and nutrient absorption via IL-22; however, little is known about how these immune cells fuel effector function. Wu et al. now report that uptake of dietary proline acts as a critical metabolic modulator of the ILC3 transcriptome and cytokine production to maintain gut health.

Glucose transporter-mediated uptake of glucose is a key metabolic checkpoint in T cells. Fu et al. have identified GLUT2 as a critical regulator of CD8⁺ T cell metabolism and function in response to glucose and oxygen availability.

Neuronal energization and memory formation in the fruit fly are found to be conditioned by the shuttling of alanine between glial cells and neurons. This observation highlights the emerging role of energy metabolism as a driver of tissue function.

Analysis of cells shed from the mouse gut, using bulk and single-cell transcriptomics, as well as single-molecule FISH and intravital imaging, revealed that shed cells are diverse, remain viable for a few hours and upregulate anti-microbial gene expression programs.

The molecular underpinnings of the extensive cellular, morphological and functional plasticity of skeletal muscle in exercise training are poorly understood. We have now begun to unravel the complex epigenetic, transcriptional and proteomic networks that determine the muscle response to exercise in a manner depending on the training state.

Bahar Halpern et al. use bulk and single-cell RNA sequencing of intestinal faecal washes to show that intestinal epithelial cells remain viable after being shed. Alongside shed immune cells, these epithelial cells may contribute to immune regulation in the intestine.

In this study, Kreuzaler et al. perform zonal analysis to study metabolic heterogeneity in breast cancer and identify the metabolic dependency on pantothenic acid (vitamin B5) in areas of the tumor that show high expression levels of the oncogene MYC. Dietary restriction of vitamin B5 reverses several MYC-driven metabolic changes and hampers tumor progression.

PDK4-dependent lactate production by senescent stromal cells is shown to promote cancer growth and drug resistance and might have a broader role in the emergence of age-associated diseases.

Kovatcheva et al. show that vitamin B₁₂ improves the efficiency of in vivo reprogramming and tissue repair through its functions in one-carbon metabolism and epigenetic modulation.

Guhathakurta et al. describe the acetyltransferase activity of MOF in the mitochondria. MOF can acetylate COX17, thus contributing to the assembly and function of respiratory complex IV. These findings provide better understanding of how mitochondrial function is fine-tuned by acetylation.

Defects in interleukin-22 production and group 3 innate lymphoid cells are correlated with aggravated gut inflammation. Wu et al. find that proline uptake via the proline transporter Slc6a7 is involved in activation of lymphoid tissue inducer cells and interleukin-22 production in the gut, and that dietary supplementation with proline alleviates colitis in a mouse model.

In this study, Fu et al. provide mechanistic insight into how GLUT2 fine-tunes environmental nutrient sensing with T cell activation, which optimizes metabolic adaptation during acquisition of T cell effector function.

Gut-derived ammonia mediates stress responses in the host by maintaining brain glutamine availability, uncovering a gut–brain signalling basis for emotional behaviour.

In this study, Rabah et al. investigate glucose usage in the brain, and show how glial cells transfer glycolysis-derived alanine to neurons in a fly model, thus supporting memory formation in cholinergic circuits.

The authors explore the molecular signature of skeletal muscle adaptations to an acute bout of exercise in mice, providing a valuable resource that includes transcriptomic, epigenetic, proteomic and phosphoproteomic changes in muscle plasticity.