title: Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae.
abstract: Anacardic acid is a medicinal phytochemical that inhibits proliferation of fungal as well as several types of cancer cells. It induces apoptotic cell death in various cell types, but very little is known about the mechanism involved in the process. Here, we used budding yeast Saccharomyces cerevisiae as a model to study the involvement of some key elements of apoptosis in the anacardic acid-induced cell death. Plasma membrane constriction, chromatin condensation, DNA degradation, and externalization of phosphatidylserine (PS) indicated that anacardic acid induces apoptotic cell death in S. cerevisiae. However, the exogenous addition of broad-spectrum caspase inhibitor Z-VAD-FMK or deletion of the yeast caspase Yca1 showed that the anacardic acid-induced cell death is caspase independent. Apoptosis-inducing factor (AIF1) deletion mutant was resistant to the anacardic acid-induced cell death, suggesting a key role of Aif1. Overexpression of Aif1 made cells highly susceptible to anacardic acid, further confirming that Aif1 mediates anacardic acid-induced apoptosis. Interestingly, instead of the increase in the intracellular reactive oxygen species (ROS) normally observed during apoptosis, anacardic acid caused a decrease in the intracellular ROS levels. Quantitative real-time PCR analysis showed downregulation of the BIR1 survivin mRNA expression during the anacardic acid-induced apoptosis.
authors.affiliation: Department of Microbiology and Biotechnology Centre, Centre for Genome Research, M. S. University of Baroda, Vadodara, 390002, India. suhail.bt@gmail.com.
authors.forename: Suhail
authors.initials: S
authors.lastname: Muzaffar
authors.affiliation: Department of Microbiology and Biotechnology Centre, Centre for Genome Research, M. S. University of Baroda, Vadodara, 390002, India.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Chattoo
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000502:physiology*; D012331:RNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D048729:Anacardic Acids; D000975:Antioxidants; C546593:Bir1 protein, S cerevisiae; D002352:Carrier Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C088115:anacardic acid; D005020:Ethyl Methanesulfonate; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases
keywords: Anacardic acid; Apoptosis inducing factor; Caspase independent apoptosis