**1. Introduction**

Caffeine (1,3,7-trimethylxanthine) is the best-known chemical constituent of coffee and one of the most widely consumed and socially accepted natural stimulants. As an important constituent of coffee, but also of other largely-consumed beverages such as tea, chocolate, and cola-like drinks, caffeine is by far the most ingested methylxanthine, along with the less representative theophylline (1,3-dimethylxanthine, encountered in tea) and theobromine (1,7-dimethylxanthine, mostly found in cocoa). Caffeine is also widely used as an important ingredient of various medicine and non-prescription drugs (used against headaches, common cold, or as appetite suppressants), sports and energy drinks, nutritional supplements, and cosmetics. The scientific literature dealing with the biological effects of caffeine is vast, revealing a large amount of evidence on both the beneficial and deleterious effects, on indications and contraindications, on adverse effects and toxicity, etc. The action of caffeine at the cellular level has been intensively investigated, and there are three fundamental mechanisms which are universally recognized: intracellular mobilization of calcium, inhibition of phosphodiesterases, and antagonism at the level of adenosine receptors [1].

Caffeine belongs to the purine alkaloid family closely linked with the bases adenine and guanine (Figure 1), which are fundamental components of nucleosides, nucleotides, and the nucleic acids [2]. Caffeine is a low-affinity adenosine and ATP analogue which interacts with a number of cellular processes, including cell growth, DNA metabolism, and cell cycle progression [3].

**Figure 1.** Chemical structures of some purines chemically related to caffeine.

In this review, we present some of the studies set to unravel the caffeine mechanisms of action using *Saccharomyces cerevisiae* as a model for the eukaryotic cell. A model organism is used in scientific research for various reasons: simplification of the biological context, overcoming ethical and experimental constraints, elimination of redundancies, the establishment of a framework for development and optimization of analytical methods, etc. Importantly, a model organism has to be representative of a larger class of living beings [4]. *S. cerevisiae,* a relatively simple unicellular eukaryote, has emerged as a versatile and robust model organism to study the fundamental factors that determine eukaryotic cell biology [5]. *S. cerevisiae* is most utilized by the research community due to its amenability to genetic studies, comprehensive genome annotation [6], and a high degree of homology of essential cellular organization and metabolism with higher eukaryotes [7]. Additionally, *S. cerevisiae* is an invaluable tool in genomic studies, resistance profiling, metabolome studies, and metabolic engineering [8–12]. *S. cerevisiae* offers insights into the complex mechanisms underlying the sensing and response to the external conditions, including exposure to a plethora of synthetic and natural chemical compounds, such as caffeine. *S. cerevisiae* is generally responsive to caffeine, as it was uncovered that this substance affects yeast cell growth and morphology, DNA repair mechanisms, intracellular calcium homeostasis, and cell cycle progression [13].

This paper provides an overview on the studies that used *S. cerevisiae* to unravel some potential effects of caffeine on the eukaryotic cells, with a focus on caffeine transport in yeast cells, caffeine influence on cells exposed to irradiation, caffeine interaction with target of rapamycin (TOR) and cell wall integrity pathways, and caffeine influence on the lifespan of the cells.
