Reviews & Analysis

Methanol is a promising feedstock owing to its low price, abundance, energy richness and renewability. However, the toxicity of methanol limits methanol-based biomanufacturing. Rescuing methylotrophic yeast from cell death by restoring phospholipid metabolism enables high-level production of free fatty acids from methanol.

Ultraviolet radiation exerts differential effects in men and women. Parikh et al. reveal that solar exposure on the skin triggers food-seeking behaviour in males, but not females, through a mechanism dependent on ghrelin secretion from skin adipocytes.

In this Perspective, Pekkurnaz and Wang offer an integrative overview on how mitochondrial homeostasis and diversity in morphology, distribution, composition and function contribute to meeting specific cellular demands, with a special focus on neurons

Busquets-García et al. provide a historical perspective of the discovery of endocannabinoid signalling and summarize the most recent findings on the role of endocannabinoids in the regulation of intracellular metabolism and its implications for whole-body homeostasis.

Anti-PD-1 immunotherapy has emerged as a revolutionary therapeutic strategy against cancer. However, it often leads to undesired side effects. In this issue, a new study reports how PD-1 signalling drives metabolic dysregulation in colonic lymphoid tissue inducer cells, thus contributing to the development of intestinal inflammation.

Hepatic inflammation is a major co-morbidity in obesity. New work shows that activated brown adipose tissue releases maresin-2, a lipid molecule derived from docosahexaenoic acid, which targets the liver and actively protects against obesity-induced hepatic inflammation.

Reactive oxygen species (ROS) have important roles in health and disease, but are chemically complex and difficult to measure accurately. This consensus statement proposes guidelines and best practices on the nomenclature and assessment of ROS, oxidative reactions and oxidative damage in cells, tissues and in vivo.

NAD⁺ is a key electron acceptor in proliferating cells, needed to increase biomass. Computational and experimental approaches demonstrate that NAD⁺ regeneration is critical for de novo lipid synthesis when exogenous sources are limited, underlying cancer cell dependence on lipids when mitochondrial respiration is reduced.

Ong et al. uncover a role for the YAP/TAZ–TEAD transcriptional pathways in retinal angiogenesis via the regulation of amino acid transporters and assessed mTORC activation. These findings establish the mechanism through which endothelial cells regulate nutrient acquisition and consumption.

Gasser et al. provide a concise overview of the known metabolic functions of endogenous FGF1 and discuss its therapeutic potential after peripheral or central administration.

Itaconate is an immunomodulatory Krebs cycle-derived metabolite. Description of two isomers of itaconate, mesaconate and citraconate, which have overlapping and distinct properties when compared with itaconate in macrophages, expands the knowledge of this intriguing family of immunomodulatory metabolites.

Ozanne and colleagues discuss the evidence of sex differences in the response to suboptimal pre-conceptual and in utero environments, detail the biological mechanisms underlying the intergenerational inheritance of metabolic traits, and show how these sex differences can manifest as metabolic disease in adults.

Activation of resting regulatory T cells (T_regs) upon antigen encounter is essential for proper T_reg function. However, the metabolic pathways that mediate this transition are unknown. Liu et al. have identified the non-oxidative pentose phosphate pathway as a central regulator of T_reg activation and function.

A glucose-like metabolite, which is reduced in the serum of diabetic patients, inhibits the entry of SARS-CoV-2 into key cellular targets. The work led by Cheng and colleagues provides a molecular explanation for the increased risk of severe COVID-19 in patients with diabetes.

Until now, the BDNF–TrkB signalling pathway was thought to be exclusively regulated by neurons. Ameroso et al. show that astrocytic TrkB.T1 is a critical substrate of BDNF in the regulation of energy balance and that its defective signalling in hypothalamic circuits leads to obesity.

Maria Ermolaeva and Liron Boyman share their scientific journeys in this instalment of Career pathways and highlight the value of mentors and collaborators, and the importance of following your research interests.

Although food-craving episodes during pregnancy are common in humans, the neural, cellular and molecular mechanisms that underlie these eating bouts remain unknown. New work points to dopamine receptor D2-expressing neurons of the reward system as critical mediators of compulsive feeding during pregnancy.

Oncometabolites are pro-tumourigenic metabolites that can determine tumour aggressiveness. This study found that methylmalonic acid is upregulated in breast lung metastasis and metastatic cancer cells. Methylmalonic acid alters the gene expression profile to induce a pro-metastatic phenotype in breast and lung cancer cells.

The clearance of dying cells by macrophages releases mediators that switch off inflammation. Ampomah et al. reveal how an amino acid derived from apoptotic cargo changes the methylation epigenome of macrophages to take the brakes off an ERK-dependent pathway that terminates inflammatory responses.

Multi-organ disease in patients seriously unwell with COVID-19 is commonly reported. However, debate exists as to whether extra-pulmonary manifestations are the result of indirect effects or of direct extra-pulmonary organ infection. Wanner et al. attempt to tackle this issue with a focus on liver tropism of the SARS-CoV-2 virus.