Reviews & Analysis

Murine blastocysts and embryonic stem cells mimicking the pre-implantation epiblast import extracellular protein through macropinocytosis and engage a robust lysosomal digestive programme to meet their nutrient demands. We found that as development proceeds, post-implantation epiblast-like cells downregulate protein digestion, increase expression of amino acid transporters and become dependent on soluble amino acids.

In nature, organisms constantly face a variety of stresses in the environment. An organism’s ability to resolve a stressful state is crucial in maintaining homeostasis. In this issue of Nature Metabolism, Wei et al. report that redox-dependent caspase cleavage of fatty acid synthase triggers a global cue for stress resolution in Caenorhabditis elegans.

Calcium sensing receptor (CaSR) and peptide transporter 1 (PepT1) have been implicated in protein sensing in the gut, although the mechanisms are poorly understood. We find that, in the small intestine, CasR and PepT1 are necessary for protein sensing to regulate gut peptide release, feeding and glucose tolerance in rats in vivo.

A study in Nature Metabolism shows that the thyroid gland contains two subtypes of thyrocytes (the cells that produce thyroid hormones) and reveals a role for Notch signalling in regulating thyrocyte homeostasis and activity, as reduced Notch activity results in hypothyroidism.

Macrophages that clear apoptotic cells (efferocytosis) proliferate to enhance tissue repair and resolution. Here, we find that a previously elucidated nucleotide ‘cargo’ proliferation pathway that increases Myc mRNA is complemented by efferocytosis-induced lactate, which stabilizes Myc protein through SIRT1-mediated Myc protein deacetylation.

The authors present an overview of the metabolism and pleiotropic actions of ketone bodies, summarizing their endogenous sources, signalling mechanisms and systemic metabolic effects.

We demonstrated increased phospholipid peroxidation due to the formation of monolysocardiolipin–cytochrome c complexes in tafazzin-deficient models of Barth syndrome. We found that a specific anti-peroxidase agent inhibited this complex and improved mitochondrial respiration. Thus, targeting the deleterious peroxidase activity offers a potential therapeutic approach to treat Barth syndrome.

The gene-editing tool mitoARCUS has been precisely fine-tuned to reduce m.3243A>G mitochondrial DNA (mtDNA) without harming wild-type mtDNA or nuclear DNA in vitro and in vivo, which paves the road to the first human trials.

This Review discusses the role of mitophagy in cellular and organismal health and disease, with a specific focus on human ageing and evidence obtained in clinical studies.

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.

Stress is an important risk factor for neuropsychiatric disorders such as major depression, but the underlying biological mechanisms remain largely unclear. A recent study has revealed a mechanism that regulates neuronal metabolism and mitochondrial function, and thereby drives stress susceptibility and disease outcomes.

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.

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.

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.

This Review article discusses how the emerging field of metabolomic epidemiology gives insight into the aetiology of various diseases and how these findings could be translated into clinical applications.

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.

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.

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.

Bilal Sheikh and Yuxiong Feng share their scientific journey and how it has taken them around the world and given them freedom to pursue their curiosity and own ideas. They share the passion that drives their research and highlight the importance of building a strong, collaborative and complementary team.

Brown adipose tissue has a crucial role in regulating body temperature in mammals. Recent research delves into the notion of thermogenic memory and identifies a subset of adipocytes that enhance the response to repeated stimulation events via de novo lipogenesis.