Forcina, G. | bioRxiv Science

bioRxiv2026

Dissecting Complex Interactions Between Ferroptosis and the Proteasome

The proteasome is an essential multiprotein complex whose inhibition can lead to apoptosis. Ferroptosis is a non-apoptotic cell death mechanism whose fundamental regulation continues to be elucidated. How proteasome function regulates ferroptosis sensitivity is poorly understood and difficult to study given the essential nature of the proteasome. Here, we isolated the effects of proteasome inhibition on ferroptosis by combining direct cell death imaging, cell death pathway-specific inhibitors, and mathematical modeling. We find that proteasome inhibition enhances sensitivity to ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition while simultaneously promoting resistance to ferroptosis induced by system x - inhibition. Sensitization to GPX4 inhibition requires protein synthesis but not the apoptosis execution machinery and is opposed by the activating transcription factor 4 (ATF4) stress response pathway. This work demonstrates a complex role for proteasome function in ferroptosis regulation and establishes new methods to dissect cross-talk between ferroptosis and essential cellular processes.

cell biology↗

bioRxiv2023

First insights into nasal microbiome in wine tasters

Over the last decades, the study of the microbiome has been receiving increasing attention as a major driver of individual health and wellbeing. The accumulation of knowledge on microbiomes sparked new research lines, from which the association between oral microbiome composition and taste perception is of great interest. Taste plays a paramount role in food and beverage choice as well as emotions. For wine tasters, the smell is also part of the tasting evaluation. However, the nasal microbiome is relatively unexplored. The relation between the microorganisms residing in the nostrils is still poorly known despite their leading role in flavor perception. Therefore, characterizing the composition of nasal microbiomes represents a fundamental prerequisite to elucidate their relationship with taste. To improve our understanding of the relationship between taste and the microorganism inhabiting the nostrils, the nasal microbiome of 5 wine tasters versus 5 non-tasters was analyzed through the sequencing of the V3-V4 region of the 16S rRNA gene. The taxonomic composition of these nasal microbiomes was characterized, and the comparison of diversity indexes revealed no significant differences. However, the experimental group showed a lower number of identified taxa (171) when compared to the control group (287). Another interesting result was the higher presence of Krebs Cycle pathways in wine tasters, which could indicate the importance of the nostril bacterial community in alcohol oxidation. Regarding smoking habits, smokers presented a lower microbiome diversity. These preliminary results should be confirmed in a larger sample dataset of wine tasters and controls.

microbiology↗