Volume 3 Issue 1, January 2021

In this instalment of Career pathways, Jing Fan and Edward A. Phelps reflect on fostering their newly formed research programs in the face of challenges both familiar and new.

Mitochondrial diseases are caused by genetic variants in either nuclear or mitochondrial DNA, and they have no known treatments. A new study by Perry et al. in this issue of Nature Metabolism used a drug screen to identify the widely available antibiotic doxycycline, an inhibitor of mitochondrial translation, as a potential pharmacological treatment for mitochondrial diseases.

Liver function depends on the temporal and zonal distribution of complementary metabolic tasks in hepatocytes. A new study by Droin et al. highlights how chronobiology and liver zonation orchestrate liver metabolism at single-cell resolution.

A creatine futile cycle has been shown to contribute to energy expenditure in beige adipocytes in preclinical mouse models of obesity. In this issue of Nature Metabolism, Connell and colleagues show that creatine supplementation in healthy young female vegetarians unfortunately affects neither human brown adipocyte activity nor cold-induced energy expenditure.

Van Gastel and Carmeliet provide an overview of emerging findings on how cellular metabolism shapes skeletal stem cell fate and function, and discuss how metabolic dysregulation might contribute to skeletal ageing and degenerative diseases.

The tumour microenvironment (TME) is a unique cellular and metabolic landscape. Elia and Haigis describe how metabolism influences, and is affected by, the complexity of cellular interactions within the TME and highlight opportunities for therapeutic intervention.

In an unbiased screen, Perry et al. find that tetracycline antibiotics improve resilience of cultured cells carrying disease-associated mitochondrial DNA mutations. Doxycycline is shown to increases survival, and reduce symptoms, in a mouse model of Leigh syndrome.

Previously, liver zonation was analysed statically, and liver chronobiology was analysed at the tissue level. Using single-cell RNA-seq and single-molecule FISH, Droin et al. study the interplay between liver gene regulation in space and time at the sub-lobular scale.

Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism.

Li et al. report a non-metabolic role of NADPH as an inhibitor of HDAC3, thus linking NADPH levels with the epigenetic state of a cell.

The localization of long non-coding RNAs plays a vital role in regulating cellular processes. In addition to compiling a database of organelle-associated lncRNAs, Sang et al. identify a role for the lncRNA GAS5 in regulating tricarboxylic acid cycle enzymes during nutrient stress.

Creatine availability is known to affect creatine-driven thermogenesis in mice. Here Connell et al. report data from a clinical trial in which daily creatine supplementation, perhaps surprisingly, did not alter thermogenesis in adults with otherwise low dietary creatine intake.