Biology subjects

Seike, T.

Publications and source records attributed to Seike, T..

9 recordsLinked to original sources

bioRxiv2026

ALDH1B1 promotes mitochondrial γ-butyrobetaine biosynthesisand fatty acid oxidation in colorectal cancer

Metabolic reprogramming is a hallmark of cancer cells, and stem-like populations often upregulate aldehyde dehydrogenases (ALDHs). Functional studies have established essential roles for individual ALDH isoforms in tumor initiation, progression, and metastasis; however, the mechanisms by which these enzymes promote malignancy remain poorly understood. Here we show that aldehyde dehydrogenase 1B1 (ALDH1B1), a mitochondrial enzyme highly expressed in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), generates {gamma}-butyrobetaine (GBB) and {gamma}-aminobutyric acid (GABA) in CRC cells. The biosynthesis of both aminocarboxylic acids has been attributed to the cytosolic enzyme ALDH9A1, and we demonstrate that mitochondrial GBB and GABA are functionally distinct from the cytosolic pools of these metabolites. We further demonstrate that mitochondrial GBB can function as an antiport substrate of carnitine-acylcarnitine translocase (CACT), the transporter that mediates fatty acid uptake into the mitochondrial inner matrix. This activity complements the role of cytosolic GBB as the biosynthetic precursor to carnitine. Accordingly, ALDH1B1 can markedly enhance mitochondrial fatty acid oxidation (FAO), a catabolic process that has been linked to CRC and PDAC stemness, progression, and metastasis. Our findings reveal an unexpected role for ALDH1B1 in carnitine metabolism, GABA biosynthesis, and FAO and illustrate how the compartmental reprogramming of metabolic pathways can promote tumor growth.

cancer biology↗

bioRxiv2026

Curcumin Enhances Alcoholic Fermentation in Yeast by Promoting Osmotic Stress Adaptation

Spices contain diverse plant secondary metabolites with antimicrobial and antioxidant activities that can influence plant-microbe interactions. Among these metabolites, curcumin and piperine are major bioactive constituents of turmeric and black pepper, respectively. In this study, we demonstrate that curcumin and piperine enhance alcoholic fermentation in the budding yeast Saccharomyces cerevisiae. Curcumin significantly promoted alcoholic fermentation under high-glucose conditions (20-40% glucose), which impose substantial osmotic stress on yeast cells. Under these conditions, curcumin enhanced yeast growth, improved osmotic stress tolerance, and increased resistance to cell wall digestion, suggesting enhanced stress adaptation during fermentation. Furthermore, deletion of HOG1, which encodes the central MAP kinase of the High-Osmolarity Glycerol (HOG) pathway responsible for the osmotic stress response, abolished the fermentation-enhancing effect of curcumin, indicating that Hog1 function is required for this effect. Consistent with this result, transcriptomic and RT-qPCR analyses revealed increased expression of stress adaptation-related genes, including known HOG pathway-responsive genes. In contrast, the expression of genes involved in amino acid catabolism was decreased at 12 h after the initiation of fermentation, while metabolomic analysis revealed increased intracellular levels of amino acids, including glutamate and asparagine, at 24 h. These coordinated transcriptional and metabolic changes are consistent with reduced amino acid catabolism and a shift toward a metabolic state favorable for sustained fermentation. Together, these findings suggest that curcumin enhances alcoholic fermentation under osmotic stress by promoting stress adaptation that supports yeast growth and sustained fermentation.

microbiology↗

bioRxiv2026

Phenotypic diversity of yeasts curated in the 5th edition of The Yeasts: A data-driven visualization approach

Yeasts have long served as key experimental systems in genetics, cell biology, and fermentation research; however, these studies have largely focused on a limited number of model species. In contrast, yeasts are a fungal group with remarkable physiological and ecological diversity. To provide a global overview of yeast diversity, we compiled and visualized phenotypic information for approximately 1,300 yeast species documented in The Yeasts (5th edition), including carbon utilization profiles, fermentation capacity, growth temperature ranges, and reported isolation sources. Taxonomic reconciliation revealed extensive reannotation, with approximately 44% of the species undergoing name changes and recognized genera increasing from 143 to 233. Integrative analyses revealed pronounced phylogenetic structuring of metabolic breadth. Many basidiomycetous yeasts, particularly Agaricomycotina, exhibited broader, generalist-like carbon utilization, whereas ascomycetous yeasts, especially Saccharomycotina, more frequently displayed sugar-centered, specialist-like narrower profiles; model yeasts such as Saccharomyces cerevisiae and Schizosaccharomyces pombe fell at the narrow end of this spectrum. Fewer than half of all species fermented glucose, a trait largely confined to Saccharomycotina. In addition, nearly one-fifth of species failed to grow at 30 {degrees}C, the standard laboratory temperature. By reconstructing and visualizing decades of dispersed taxonomic knowledge accumulated in The Yeasts, this study reframes yeasts not merely as laboratory model organisms but as metabolically diverse fungi whose phenotypic diversity reflects diverse ecological contexts. The analytical framework presented here provides a foundation for integrating standardized quantitative phenotypes and newly described species and offers a starting point for exploring the latent ecological and metabolic potential of yeast diversity.

microbiology↗

bioRxiv2026

Constitutive sporulation in wild fission yeast enhances insect-mediated survival

Sexual reproduction in yeast typically occurs under nutrient-limited conditions, producing stress-resistant spores that promote survival. However, wild Schizosaccharomyces japonicus strains isolated from fruit flies exhibit constitutive sporulation even under nutrient-rich conditions. Here we demonstrate that this nutrient-independent sporulation enhances survival by enabling spores to resist digestion by Drosophila melanogaster, and that although such strains are disadvantageous under nutrient-rich conditions, they are positively selected during insect predation. Genetic analyses reveal that multiple mutations in six meiotic regulatory genes, acting via epistasis, underlie this phenotype. This trait is widely distributed across natural populations throughout Japan. These findings suggest that constitutive sexual reproduction functions as an adaptive strategy facilitating insect-mediated dispersal, reflecting an ecological context where sexual reproduction is maintained despite its costs. This work provides new insights into yeast-insect symbiosis, evolutionary dynamics of sexual adaptation, and potential applications in yeast breeding.

evolutionary biology↗

bioRxiv2025

Context-dependent activation and evolutionary buffering of a mating pheromone in fission yeast

The evolution of mating signals drives reproductive isolation and speciation across diverse lineages. However, how short peptide pheromones, typically subject to strong structural constraints, achieve functional diversification remain unclear. In the fission yeast Schizosaccharomyces pombe, a previously established library of 153 single-amino acid variants of the mating pheromone M-factor was applied to large-scale competition assays under varied mating conditions. Mutations deleterious under standard conditions became advantageous at specific environmental pH levels, demonstrating context-dependent pheromone function activation. Synthetic peptide assays confirmed that certain substitutions act as environmental molecular switches. Comparative analysis with the closely related Schizosaccharomyces octosporus species identified a permissive mutation that mitigates the effects of otherwise inactivating changes, enabling an evolutionary route without intermediate fitness loss. Our findings reveal how short peptide signals evolve via environmentally contingent activation and compensatory interactions, offering a mechanistic framework for understanding the ecological and evolutionary dynamics of mating communication.

evolutionary biology↗

bioRxiv2025

Conserved metabolic adaptation mechanisms in cancer cells and yeast against mitochondrial dysfunction indicate an additional role of aerobic glycolysis for cell survival

Eukaryotic cells primarily generate ATP through oxidative phosphorylation and substrate-level phosphorylation. Despite the superior efficiency of oxidative phosphorylation, eukaryotic cells often utilize both pathways as aerobic glycolysis even in the presence of oxygen. However, its role in cell survival remains poorly understood. In this study, aerobic glycolysis of the Warburg effect in breast cancer cells (MCF7) and the Crabtree effect in a laboratory strain of Saccharomyces cerevisiae (S288C) were compared following treatment with electron transport chain inhibitors, including FCCP, antimycin A, and oligomycin. MCF7 and S288C exhibited strikingly similar metabolic rewiring toward substrate-level phosphorylation against the inhibitor treatment, suggesting that mitochondrial oxidative phosphorylation and cytosolic substrate-level phosphorylation communicate through a common mechanism. Measurements of mitochondrial membrane potential (MMP) and ATP concentration further indicated that cytosolic ATP was transported into the mitochondria under conditions of reduced electron transport chain activity. This ATP was likely utilized by the reverse mode of H+/ATPase to maintain the MMP which contributed to avoiding programmed cell death. These results suggest that the ATP supply to mitochondria plays a conserved role in aerobic glycolysis across yeast and mammalian cancer cells. This mechanism likely contributes to cell survival under conditions of fluctuating oxygen availability.

cell biology↗

bioRxiv2020

Distinct specificity of two pheromone G-protein coupled receptors, Map3 and Mam2, in fission yeast species.

Most sexually reproducing organisms have the ability to recognize individuals of the same species. In ascomycetes including yeasts, potential mating between cells of opposite mating-type depends on the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors (GPCRs). Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation, very few studies have focus on the differences in pheromone/receptor system between mating types. The fission yeast Schizosaccharomyces pombe has two mating types (sexes), Plus (P) and Minus (M). Here we investigated the specificity of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor, in fission yeast. First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus, which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable. Next, we swapped individual domains of Mam2 and Map3 with the respective domains in SoMam2 and SoMap3, which revealed differences between the receptors both in the intracellular regions that regulate the downstream signaling of pheromones and in the molecular recognition for pheromone binding. In particular, we demonstrated that two amino acid residues of Map3, F214 and F215, are essential for the specificity of M-factor recognition. Thus, the differences in these two GPCRs are likely to reflect the significantly distinct specificities of their respective pheromone/receptor systems; that is, the specificity of Map3 is more stringent than that of Mam2. We speculate that this sexual asymmetry might allow ascomycete fungi to generate novel prezygotic barriers within a population, while maintaining strong mate choice. Our genetic analyses also contribute to our understanding of the receptors that comprise the Class D GPCRs belonging to the fungal pheromone receptor family. Author summaryCourtship signals play a key role in the fertilization processes of living beings from animals to microorganisms and, in particular, sex pheromones are involved in differentiating among species. On the other hand, changes in a pheromone/receptor system might also alter species-specificity during the selection of a mating partner, which is likely to facilitate prezygotic isolation. Here we demonstrate a distinct difference in the specificity of GPCRs for pheromones between cells of opposite mating-type in the fission yeast Schizosaccharomyces pombe, by conducting a comprehensive genetic analysis and comparison of these proteins between closely related fission yeast species. Our finding of sexual asymmetry due to the relative strictness of receptors in S. pombe suggests that it might be one of the driving forces behind the formation of new species. Such differences in pheromone/receptor interactions between the sexes may occur in a variety of life-forms such as insects and amphibians; hence, the findings of this study might be extended to other organisms. In addition, this study of S. pombe pheromone receptors sheds light on the functions of the unique Class D GPCRs.

genetics↗

bioRxiv2019

The asymmetric chemical structures of two mating pheromones reflect their differential roles in conjugation of Schizosaccharomyces pombe

In the fission yeast Schizosaccharomyces pombe, the mating reaction is controlled by two mating pheromones, M-factor and P-factor, secreted by M- and P-type cells, respectively. M-factor is a C-terminally farnesylated lipid peptide, whereas P-factor is a simple peptide. To examine whether this chemical asymmetry in the two pheromones is essential for conjugation, we constructed a mating system in which either pheromone can stimulate both M- and P-cells, and examined whether the resulting autocrine strains can mate. Autocrine M-cells responding to M-factor successfully mated with P-factor-less P-cells, indicating that P-factor is not essential for conjugation; by contrast, autocrine P-cells responding to P-factor were unable to mate with M-factor-less M-cells. The sterility of the autocrine P-cells was completely recovered by expressing the M-factor receptor. These observations indicate that the different chemical characteristics of the two types of pheromone, a lipid and a simple peptide, are not essential; however, a lipid peptide is absolutely required for successful mating. Our findings allow us to propose a model of the differential roles of M-factor and P-factor in conjugation of S. pombe. Summary statementLipid pheromone peptides secreted locally from one cell may be concentrated at the fusion site with an opposite mating-type cell, which then polarizes to enable successful conjugation in S. pombe.

cell biology↗

bioRxiv2018

Asymmetric Diversification of Mating Pheromones in Fission Yeast

In fungi, mating between partners critically depends on the molecular recognition of two peptidyl mating pheromones by their respective receptors. The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M), which secrete two different mating pheromones: P-factor recognized by Mam2, and M-factor recognized by Map3, respectively. Our recent study demonstrated that a few mutations in both M-factor and Map3 can trigger reproductive isolation, a cause of speciation, in S. pombe. Here we explored the mechanism underlying reproductive isolation through genetic changes of pheromones and receptors. We investigated the diversity of genes encoding the pheromones and their receptor in 150 S. pombe wild strains. Whereas the amino acid sequences of M-factor and Map3 were completely conserved, those of P-factor and Mam2 were very diverse. In addition, the P-factor gene contained varying numbers of tandem repeats of P-factor (4-8 repeats). We also explored the recognition specificity of pheromones between S. pombe (Sp) and its close relative Schizosaccharomyces octosporus (So). So-M-factor did not have an effect on S. pombe P-cells, but So-P-factor had a partial effect on S. pombe M-cells, allowing them to mate successfully. Thus, recognition of M-factor seems to be tight, whereas that of P-factor is relatively loose. Moreover, diversity of P-factor and Mam2 might be due to a P-factor-specific peptidase. Overall, the asymmetric system for pheromone recognition in yeasts seems to allow flexible adaptation to mutational changes in the combination of pheromone and receptor while maintaining tight recognition for mating partners.

microbiology↗