In this issue of Molecular Cell, Byun et al. (2020) find that the dual targeting of glutamine metabolism and the PD-L1 checkpoint inhibitor augments anti-tumor immunity. Mechanistically, decreased glutamine availability attenuated S-glutathionylation of SERCA, resulting in an increase in cytosolic calcium, enhanced NF-κB activity, and upregulation of programmed death-ligand 1.

In this issue of Molecular Cell, Sun et al. (2020) identify ERK-mediated phosphorylation of the m6A methyltransferase complex as a regulatory mechanism for m6A and pluripotency and highlight the potential of this interaction as a target for cancer therapy.

Bilokapic at al. (2020) capture PARP2 and its accessory factor HPF1 bridging a DNA break between two nucleosomes, providing a captivating view of the context in which PARP2/HPF1 employ ADP-ribose protein modification to coordinate DNA repair and alter chromatin structure.

Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms

Li et al. (2020) elucidate the resistance mechanisms to small-molecule inhibitors targeting the G2/M cell cycle checkpoint kinase, CHK1, in a variety of non-small cell lung cancer cell lines using CRISPR-mediated genetic approaches and identify biomarkers of response.

In this issue of Molecular Cell, Wang et al. (2020a) present near-atomic resolution cryoEM structures of a proton-pumping vacuolar ATPase from human cells, illuminating the glycosylation of integral subunits and identifying a novel and conserved glycolipid ligand.

Recent work by Licznerski et al. suggests that mutant FMRP linked to Fragile-X syndrome elevates the inner mitochondrial membrane proton leak, leading to increased metabolism and changes in protein synthesis that trigger impaired synaptic maturation and autistic behaviors.

Metabolism reprogramming is critical for both cancer progression and effective immune responses in the tumor microenvironment. Amino acid metabolism in different cells and their cross-talk shape tumor immunity and therapy efficacy in patients with cancer. In this review, we focus on multiple amino acids and their transporters, solute carrier (SLC) members. We discuss their involvement in regulation