An et al. show that mis-localization of amyloid precursor protein (APP; red) into adipocyte mitochondria (green; orange indicates colocalization) promotes obesity by impairing mitochondrial protein import and mitochondrial function.

See Y. A. An et al.

Release of the neurotransmitter GABA from β-cells is known to regulate insulin secretion. Menegaz et al. now show that GABA is released directly from the cytosol in a pulsatile manner via volume regulatory anion channels and is subsequently taken up by the GABA-permissive taurine transporter TauT. Depicted is a pair of human β-cells immunostained for insulin (red) and α-tubulin (blue).

See Menegaz et al.

Mitochondrial DNA (mtDNA) replication stress in mtDNA mutator mice causes DNA damage (yellow dots) in spermatoid progenitors (turquoise nuclei), thus suggesting that defects in nuclear genome maintenance might be a unified mechanism for mouse progerias.

See Hämäläinen et al.

Here, the authors show that phospholipids influence whole-body metabolic rate and counteract obesity by altering calcium signalling and inducing energy expenditure in muscle.

See Verkerke et al.

Lee et al. show that cold temperatures delay ageing of germ stem cells and extend the fertility period of C. elegans. The cover image shows worms with coloured somatic tissues and germ line, including oocytes and fertilized eggs ready to be laid and hatched.

See Lee et al.

Vardhana et al. show that decreased dependence on exogenous glutamine is a generalizable feature of self-renewing pluripotent stem cells that can be exploited to select in vitro cultures for mouse and human pluripotent stem cells with high self-renewal potential.

See Vardhana et al.

Salem and colleagues demonstrate that leader β-cells respond first to glucose, and glucose increases β-cell calcium dynamics and connectivity between the leader and non-leader β-cells.

See Salem et al.

Iron homeostasis is tightly orchestrated to avoid toxic iron overloading. Here Lim and colleagues show that iron excess activates Nrf2 via mitochondrial ROS, thus enhancing expression of Bmp6 in liver sinusoidal endothelial cells, which in turn promotes hepcidin expression by hepatocytes, decreasing systemic iron levels.

See Lim et al.

This study characterizes multi-omic signatures that are associated with the hypoxia status of cancer cells and correlate with drug resistance or drug sensitivity, thus contrasting the conventional view that hypoxia confers drug resistance. Ninety-one percent of clinically actionable genes may be affected by hypoxia status.

See Ye et al.

The oxidative pentose phosphate pathway (oxPPP) is a major NADPH producer. Rabinowitz and colleagues show that malic enzyme or isocitrate dehydrogenase can support the growth of cells lacking the oxPPP, but the oxPPP is necessary to maintain a normal NADPH/NADP ratio, DHFR activity and folate metabolism.

See Chen et al.

Hypothalamic melanocortin neurons control energy homeostasis by modulating appetite. Here the authors reveal a role of the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

See Quarta et al.

Endothelial cells require glycolysis during angiogenesis; however, the function of the mitochondrial respiratory chain during this process is unclear. Here the authors show that mitochondrial respiration in endothelial cells is required for angiogenesis as the biosynthetic role of mitochondria is needed for endothelial cell proliferation.

See Diebold et al.