**Lavinia Liliana Ruta and Ileana Cornelia Farcasanu \***

Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Sos. Panduri 90-92, 050663 Bucharest, Romania; lavinia.ruta@chimie.unibuc.ro

**\*** Correspondence: ileana.farcasanu@chimie.unibuc.ro; Tel.: +40-721-067-169

Received: 7 July 2020; Accepted: 10 August 2020; Published: 13 August 2020

**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.

**Keywords:** caffeine; *Saccharomyces cerevisiae*; irradiation; DNA damage; TOR; signaling; lifespan
