Saccharomyces cerevisiae and Caffeine Implications on the Eukaryotic Cell

Abstract

Caffeine–a methylxanthine analogue of the purine bases adenine and guanine–is by far the most consumed neuro-stimulant, being the active principle of widely consumed beverages such as coffee, tea, hot chocolate, and cola. While the best-known action of caffeine is to prevent sleepiness by blocking the adenosine receptors, caffeine exerts a pleiotropic effect on cells, which lead to the activation or inhibition of various cell integrity pathways. The aim of this review is to present the main studies set to investigate the effects of caffeine on cells using the model eukaryotic microorganism Saccharomyces cerevisiae, highlighting the caffeine synergy with external cell stressors, such as irradiation or exposure to various chemical hazards, including cigarette smoke or chemical carcinogens. The review also focuses on the importance of caffeine-related yeast phenotypes used to resolve molecular mechanisms involved in cell signaling through conserved pathways, such as target of rapamycin (TOR) signaling, Pkc1-Mpk1 mitogen activated protein kinase (MAPK) cascade, or Ras/cAMP protein kinase A (PKA) pathway.

The monothiol glutaredoxin Grx4 influences thermotolerance, cell wall integrity, and Mpk1 signaling in Cryptococcus neoformans

“…The detergent SDS disrupts the plasma membrane, whereas CFW and Congo Red interfere with the synthesis of cell wall polysaccharides ( Elorza et al 1983 ; Wood and Fulcher 1983 ; Dichtl et al 2016 ; Liu et al 2021 ). Caffeine has a variety of targets in fungi including target of rapamycin (TOR) signaling and components of the CWI pathway ( Ruta and Farcasanu 2020 ). The grx4Δ mutants exhibited increased sensitivity to SDS, caffeine and CFW indicating that Grx4 is required for membrane and CWI; the Grx4 reconstituted strain restored growth to the WT level ( Figure 1 ).…”

“…A similar pattern was detected in the grx4Δ mutant strain with a somewhat weaker signal at 30 min of caffeine treatment, and an even weaker signal at 120 and 150 min. It is known that caffeine has additional influences on cellular functions beyond an impact on the CWI pathway ( Ruta and Farcasanu 2020 ). A different pattern of phosphorylation was observed upon treatment with SDS ( Figure 4C ).…”

Investigation of the Effects of Autophagy Signaling on the Transcription of Yeast Retrotransposon Ty2-917

“…Caffeine has multiple effects on eukaryotic cells. Although it is a specific inhibitor of TOR1 kinase, it also triggers ERAD mediated apoptosis (31). It also has a dramatic effect on DNA repair, cell wall integrity, and telomerase activity (31).…”

“…Intracellular events that activate autophagy are misfolded protein accumulations and damaged or dysfunctional cell components. Extracellular factors that activate autophagy are different chemicals and environmental cues such as amino acid starvation and nitrogen limitations (31,32). Autophagy processes can be classified into different sub-groups depending on reaction mechanisms.…”

Coffee and Caffeine Consumption for Human Health

“…Ruta and Farcasanu reviewed the studies evaluating the molecular mechanisms of action of caffeine in Saccharomyces cerevisiae as a simple model of eukaryotic cell. In addition to its three well-known mechanisms, namely intracellular mobilization of calcium, inhibition of phosphodiesterases and antagonism of adenosine receptors, the studies performed in this yeast model have confirmed that the pleiotropic effects of caffeine involve also key molecular mechanisms related with DNA repair mechanisms, cancer, and aging [ 20 ]. In contrast, Kolb et al reviewed the mechanisms that might contribute to explain the beneficial effects of habitual coffee consumption on health.…”