Two for the price of one: itaconate and its derivatives as an anti-infective and anti-inflammatory immunometabolite.

The metabolite itaconate (ITA) and its derivatives, both chemically synthesized and endogenous, have emerged as immunoregulators, with roles in limiting inflammation but also having effects on bacterial and viral infection. Some members of the ITA family have been shown to target and inhibit multiple processes in macrophages with recently identified targets, including NLRP3, JAK1, ten-eleven translocation-2 dioxygenases, and TFEB, a key transcription factor for lysosomal biogenesis. They have also been shown to target multiple bacteria, inhibiting their replication, as well as having antiviral effects against viruses such as SARS-CoV2, Zika virus, and Influenza virus.

The role of itaconate in host defense and inflammation.

Macrophages exposed to inflammatory stimuli including LPS undergo metabolic reprogramming to facilitate macrophage effector function. This metabolic reprogramming supports phagocytic function, cytokine release, and ROS production that are critical to protective inflammatory responses. The Krebs cycle is a central metabolic pathway within all mammalian cell types.

Bridging the gap - a new role for STAT3 in TLR4-mediated metabolic reprogramming.

Balic et al. describe a new role for STAT3 in TLR4 signalling in macrophages, linking LPS mediated activation of this innate immune receptor to phosphorylation of mitochondrial STAT3, resulting in distinct metabolic reprogramming.

TCA cycle signalling and the evolution of eukaryotes.

A major question remaining in the field of evolutionary biology is how prokaryotic organisms made the leap to complex eukaryotic life. The prevailing theory depicts the origin of eukaryotic cell complexity as emerging from the symbiosis between an α-proteobacterium, the ancestor of present-day mitochondria, and an archaeal host (endosymbiont theory). A primary contribution of mitochondria to eukaryogenesis has been attributed to the mitochondrial genome, which enabled the successful internalisation of bioenergetic membranes and facilitated remarkable genome expansion.

GOTcha: lncRNA-ACOD1 targets metabolism during viral infection.

Long-noncoding RNAs (lncRNAs) are emerging as important regulators of cellular processes, but few have been functionally characterized in host-pathogen interactions. A recent report in Science demonstrates a mechanistic role for a novel lncRNA in directly binding an essential metabolic enzyme, glutamic-oxaloacetic transaminase (GOT2); this interaction benefits viral replication via alteration of host metabolism.