[Abstract unavailable

The budding yeast Saccharomyces cerevisiae possesses a very flexible and complex programme of gene expression when exposed to several environmental challenges. Homeostasis is achieved through a highly coordinated mechanism of transcription regulation involving several transcription factors, each one acting singly or in combination to perform specific functions. Here, we review our current knowledge of the function of the Yap transcription factors in stress response. They belong to b-ZIP proteins comprising eight members with specificity at the DNA-binding domain distinct from that of the conventional yeast AP-1 factor, Gcn4. We finish with new insights into the links of transcriptional networks controlling several cellular processes. The data reviewed in this article illustrate how much our comprehension of the biology of Yap family involved in stress response has advanced, and how much research is still needed to unravel the complexity of the role of these transcriptional factors. The complexities of these regulatory interactions, as well as the dynamics of these processes, are important to understand in order to elucidate the control of stress response, a highly conserved process in eukaryotes.

The budding yeast Saccharomyces cerevisiae has developed several mechanisms to avoid either the drastic consequences of iron deprivation or the toxic effects of iron excess. In this work, we analysed the global gene expression changes occurring in yeast cells undergoing iron overload. Several genes directly or indirectly involved in iron homeostasis showed altered expression and the relevance of these changes are discussed. Microarray analyses were also performed to identify new targets of the iron responsive factor Yap5. Besides the iron vacuolar transporter CCC1, Yap5 also controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of Aft1 nuclear localization. Consistently, we show that in the absence of Yap5 Aft1 nuclear exclusion is slightly impaired. These studies provide further evidence that cells control iron homeostasis by using multiple pathways.

Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels.

Yeast, and especially Saccharomyces cerevisiae, are continuously exposed to rapid and drastic changes in their external milieu. Therefore, cells must maintain their homeostasis, which is achieved through a highly coordinated gene expression involving a plethora of transcription factors, each of them performing specific functions. Here, we discuss recent advances in our understanding of the function of the yeast activator protein family of eight basic-leucine zipper trans-activators that have been implicated in various forms of stress response.

BackgroundAgeing can be simply defined as the process of becoming older, which is genetically determined but also environmentally modulated. With the continuous increase of life expectancy, quality of life during ageing has become one of the biggest challenges of developed countries. The quest for a healthy ageing has led to the extensive study of plant polyphenols with the aim to prevent age-associated deterioration and diseases, including neurodegenerative diseases. The world of polyphenols has fascinated researchers over the past decades, and in vitro, cell-based, animal and human studies have attempted to unravel the mechanisms behind dietary polyphenols neuroprotection.MethodsIn this review, we compiled some of the extensive and ever-growing research in the field, highlighting some of the most recent trends in the area.ResultsThe main findings regarding polypolyphenols neuroprotective potential performed using in vitro, cellular and animal studies, as well as human trials are covered in this review. Concepts like bioavailability, polyphenols biotransformation, transport of dietary polyphenols across barriers, including the blood-brain barrier, are here explored.ConclusionThe diversity and holistic properties of polypolyphenol present them as an attractive alternative for the treatment of multifactorial diseases, where a multitude of cellular pathways are disrupted. The underlying mechanisms of polypolyphenols for nutrition or therapeutic applications must be further consolidated, however there is strong evidence of their beneficial impact on brain function during ageing. Nevertheless, only the tip of the iceberg of nutritional and pharmacological potential of dietary polyphenols is hitherto understood and further research needs to be done to fill the gaps in pursuing a healthy ageing.

Human Vps13 proteins are associated with several diseases, including the neurodegenerative disorder Chorea-acanthocytosis (ChAc), yet the biology of these proteins is still poorly understood. Studies in Saccharomyces cerevisiae, Dictyostelium discoideum, Tetrahymena thermophila and Drosophila melanogaster point to the involvement of Vps13 in cytoskeleton organization, vesicular trafficking, autophagy, phagocytosis, endocytosis, proteostasis, sporulation and mitochondrial functioning. Recent findings show that yeast Vps13 binds to phosphatidylinositol lipids via 4 different regions and functions at membrane contact sites, enlarging the list of Vps13 functions. This review describes the great potential of simple eukaryotes to decipher disease mechanisms in higher organisms and highlights novel insights into the pathological role of Vps13 towards ChAc.

Alzheimer's (AD) and Parkinson's (PD) diseases are the two most common causes of dementia in aged population. Both are protein-misfolding diseases characterized by the presence of protein deposits in the brain. Despite growing evidence suggesting that oxidative stress is critical to neuronal death, its precise role in disease etiology and progression has not yet been fully understood. Budding yeast Saccharomyces cerevisiae shares conserved biological processes with all eukaryotic cells, including neurons. This fact together with the possibility of simple and quick genetic manipulation highlights this organism as a valuable tool to unravel complex and fundamental mechanisms underlying neurodegeneration. In this paper, we summarize the latest knowledge on the role of oxidative stress in neurodegenerative disorders, with emphasis on AD and PD. Additionally, we provide an overview of the work undertaken to study AD and PD in yeast, focusing the use of this model to understand the effect of oxidative stress in both diseases.