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Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae

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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.

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Acknowledgements

We thank the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India for the financial support. Suhail Muzaffar would like to thank European Molecular Biology Organisation (EMBO) for the short-term fellowship. We would like to acknowledge Prof. Frank Madeo, University of Graz (Austria) and Prof. Stephen P. Jackson, University of Cambridge (UK) for providing us the yeast strains used in this study.

Author contributions

SM designed and performed the experiments. BBC was involved in the critical analysis of the work.

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  1. Department of Microbiology and Biotechnology Centre, Centre for Genome Research, M. S. University of Baroda, Vadodara, 390002, India

    Suhail Muzaffar & Bharat B. Chattoo

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  1. Suhail Muzaffar
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  2. Bharat B. Chattoo
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Correspondence to Suhail Muzaffar.

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This article does not contain any studies with human or animals subjects.

Additional information

Bharat B. Chattoo—deceased.

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Muzaffar, S., Chattoo, B.B. Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae . Apoptosis 22, 463–474 (2017). https://doi.org/10.1007/s10495-016-1330-6

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