MDM2 and MDMX, negative regulators of the tumor suppressor p53, can work separately and as a heteromeric complex to restrain p53's functions. MDM2 also has pro-oncogenic roles in cells, tissues, and animals that are independent of p53. There is less information available about p53-independent roles of MDMX or the MDM2-MDMX complex. We found that MDM2 and MDMX facilitate ferroptosis in cells with or without p53. Using small molecules, RNA interference reagents, and mutant forms of MDMX, we found that MDM2 and MDMX, likely working in part as a complex, normally facilitate ferroptotic death. We observed that MDM2 and MDMX alter the lipid profile of cells to favor ferroptosis. Inhibition of MDM2 or MDMX leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q 10 , an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis. Moreover, we found that PPARα activity is essential for MDM2 and MDMX to promote ferroptosis, suggesting that the MDM2-MDMX complex regulates lipids through altering PPARα activity. These findings reveal the complexity of cellular responses to MDM2 and MDMX and suggest that MDM2-MDMX inhibition might be useful for preventing degenerative diseases involving ferroptosis. Furthermore, they suggest that MDM2/MDMX amplification may predict sensitivity of some cancers to ferroptosis inducers.

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We present a transition-metal complex containing a Pt center, large aromatic ligand, and Mo-binding terminal group, designed to maximize the dispersion of individual molecules across the 2D MoS2 substrate. The bulky organic ligand structure shows higher thermal stability than typical halides in inorganic Pt salt, such as H2PtCl6, and thus provides a large number of isolated single Pt atoms on 2D surfaces even after thermal annealing up to 900 °C. Epitaxially aligned Pt nanocrystals that are 3–5 nm in diameter are also formed upon the thermal treatment, displaying different shapes (i.e., 2D vs 3D clusters), resulting from the different atomic diffusion mechanism based on each Pt precursor. The successful generation of abundant single Pt atom sites on MoS2 surface using a large complex precursor indicates the significance of precursor design for reducing the noble metal loading in various catalysis materials.

The self‐assembly of bowlic supramolecules on graphene surface is studied with single molecular sensitivity. This is achieved by incorporating a heavy metal tag in the form of a single W atom into the tip of the molecular structure, which enables the direct imaging of molecular distribution using annular dark‐field scanning transmission electron microscopy (ADF‐STEM) along with graphene as an electron transparent support. The bowlic molecules have nonplanar geometry, and their orientations with respect to their graphene substrate and with each other result in various packing configurations. Statistical data on intermolecular distances is obtained from numerous measurements of the bright contrast from the single metal atom tags. The analysis shows that the bowlic molecules lie sideways on the graphene surface with favorable head‐to‐tail stacking, rather than sitting vertically with the bowl facing toward the graphene surface. In thicker film regions, nanoscale lamellar fringes are observed, demonstrating that large‐scale aligned packing extends into 3D. Image simulations and various molecular packing schemes are discussed to help interpret the ADF‐STEM images and the possible range of molecular interactions occurring. These results aid the understanding of nonplanar supramolecular assemblies on van der Waals surfaces for potential applications in molecular recognition by porous films.

The non-invasive nature of NMR offers a means to monitor biochemical reactions in situ at the atomic-level. We harness this advantage to monitor a complex chemoenzymatic reaction that sequentially modifies reagents and loads the product on a nonribosomal peptide synthetase carrier protein. We present a protocol including a novel pulse sequence that permits to assess both the integrity of reagents and the completion of each step in the reaction, thus alleviating otherwise time-consuming and costly approaches to debug and repeat inefficient reactions. This study highlights the importance of NMR as a tool to establish reliable and reproducible experimental conditions in biochemical studies.Graphical Abstract