4 research outputs found
PELE: the Planetary Analogs & Exobiology Lava Tube Expedition
Lava tubes on Earth represent some of the most enticing Martian analog environments when investigating the possibility of past or present life on Mars. Lava tubes provide stable, sheltered environments which are isolated and protected from the radiation on the surface. The microbial mats in these caves further regulate the environment for life, allowing various microbial communities with different metabolisms to coexist. This adaptation is so successful, one could imagine it might occur on other planets, with other biologies, and perhaps with other fundamental chemistries [1]. The PELE team has investigated lava caves on Terceira Island, the Azores, and in Iceland. The project aims to correlate biological and mineralogical data to describe the interactions between the microbes and their geological substrates, to identify microbe-specific speleothems as biosignatures (Figure 1), to map the gradients of light, nutrients, and biodiversity, and to develop a sampling technique in these fragile environments. This is achieved with a combination of DNA sequencing, mass spectrometry, and XRF, XRD, and Raman spectroscopy. The work will serve as an indication of what kind of life, or remnants of life, we might expect to find in lave tubes on Mars
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MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling
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 Q10, 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