Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here.

The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.

Background/Objectives: Translation and the formation of membraneless organelles are linked mechanisms to promote cell stress surveillance. LncRNAs responsive to ethanol stress transcr_9136 of the SEY6210 strain and transcr_10027 of the BY4742 strain appear to act on tolerance to ethanol in these strains. Here, we investigate whether the ethanol responsiveness of transcr_9136 and transcr_10027 and their role in ethanol stress are associated with protein biogenesis and membraneless organelle assembly. Methods: SEY6210 transcr_9136∆ and BY4742 transcr_10027∆ and their wild-type counterparts were subjected to their maximum ethanol-tolerant stress. The expression of the transcr_9136, transcr_10027, ILT1, RRP1, 27S, 25S, TIR3, and FAA3 genes was accessed by qPCR. The level of DCP1a, PABP, and eIF4E proteins was evaluated by Western blotting. Bioinformatics analyses allowed us to check whether transcr_9136 may regulate the expression of RRP1 and predict the interaction between transcr_10027 and Tel1p. The cell death rate of SEY6210 strains under control and ethanol stress conditions was assessed by flow cytometry. Finally, we evaluated the total protein yield of all strains analyzed. Results: The results demonstrated that transcr_9136 of SEY6210 seems to control the expression of RRP1 and 27S rRNA and reduce the general translation. Furthermore, transcr_9136 seems to act on cell membrane integrity. Transcr_10027 of BY4742 appears to inhibit processing body formation and induce a general translation level. Conclusions: This is the first report on the effect of lncRNAs on yeast protein synthesis and new mechanisms of stress-responsive lncRNAs in yeast, with potential industrial applications such as ethanol production.

Malnutrition remains a major global socioeconomic challenge. When it occurs during critical developmental windows (pregnancy and lactation), it can impair maternal health and predispose offspring to long-term diseases, a central concept within the Developmental Origins of Health and Disease (DOHaD). Maternal Protein Restriction (MPR) is a widely used experimental model in this field and is known to disrupt multiple organs and systems in the offspring, increasing susceptibility to metabolic disorders. However, the cellular pathways underlying these outcomes remain insufficiently explored, particularly vesicular transport and the endomembrane system. This review examined the effects of MPR on organelles related to vesicular dynamics. Following predefined inclusion and exclusion criteria, 20 PubMed articles were selected, addressing MPR-induced alterations in the cytoskeleton, endoplasmic reticulum (ER), Golgi, endocytosis, and exocytosis. Overall, evidence indicates that MPR disrupts cytoskeletal integrity—affecting actin networks in renal, adipose, muscle, and neural cells. MPR compromises ER and Golgi activities in several organs. In the placenta, endocytic activity was consistently elevated (macropinocytosis). Exocytosis was also perturbed, contributing to lipid accumulation and inflammation. Systemically, MPR altered circulating amino acid levels, impaired hematological parameters, reduced leukocyte migration, and enhanced placental amino acid transport. These findings demonstrate that MPR destabilizes cytoskeletal architecture, ER–Golgi function, and vesicular transport across multiple offspring tissues, identifying the endomembrane system as a critical target of developmental programming. These alterations suggest persistent vulnerabilities in cellular homeostasis. Therefore, we propose the term maternal diet–dependent cellular-vesicular disorders (MDCVD), establishing a conceptual framework for future mechanistic and translational studies.

Epidemiological and experimental evidence indicate that disturbances during pregnancy or lactation can induce metabolic programming in offspring, increasing lifelong disease risk. Maternal malnutrition, whether by excess or deficiency, is linked to metabolic disorders such as type 2 diabetes, obesity, and cardiovascular diseases. Current research aims to identify biomarkers of the developmental origins of health and disease (DOHaD). Among these, peroxiredoxins (PRDX1–6) have gained attention for their mitochondrial, cytoplasmic, and endoplasmic reticulum roles in antioxidant defense, inflammation, and energy metabolism. This scoping review aimed to understand what is known about the effects of maternal malnutrition on the PRDXs in different organs in the offspring, to understand whether these biomolecules have a potential role in the DOHaD context. This review followed PRISMA-ScR guidelines and systematically searched PubMed studies linking maternal nutritional undernutrition or overnutrition to PRDX expression in offspring. Only studies directly assessing PRDXs after maternal dietary interventions were included; reviews, preprints, and studies without maternal influence were excluded. Therefore, we identified 426 manuscripts, of which 346 were removed for being outside the scope of the review, 41 for being duplicates, 1 for not reporting the effect on PRDXs, 21 for not being related to maternal diet, 2 were review articles, and 1 was used as a model of maternal stress. Therefore, a total of 14 manuscripts were selected, all of an experimental nature. Maternal malnutrition affects different PRDX isoforms in several models and organs, outlining possible disorders associated with cellular function and stress response. Therefore, maternal undernutrition affects cardiac, cerebral, hepatic, ovarian, pancreatic, and adrenal PRDXs, while maternal overnutrition affects PRDXs in the salivary glands, intestine, and ovaries, establishing possible metabolic and reproductive risks through biological mechanisms that still need to be thoroughly investigated. We highlighted numerous gaps in the literature and provided a solid foundation for future experimental and translational studies that will establish whether PRDXs are biomarkers of the developmental origins of diseases and maternal malnutrition.